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| Open AccessTAD border deletion at the Kit locus causes tissue-specific ectopic activation of a neighboring gene
Research on the Kit locus shows TAD boundary deletion may or may not trigger ectopic gene activation in different cell types, influenced by active enhancers’ position relative gene promoters.
- Evelyn Kabirova
- , Anastasiya Ryzhkova
- & Nariman Battulin
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Article
| Open AccessStructural domain in the Titin N2B-us region binds to FHL2 in a force-activation dependent manner
Titin N2B unique sequence (N2B-us) is a 572 amino acid sequence that acts as an elastic spring to regulate muscle passive elasticity. Here the authors identify a mechanosensitive structural domain within the titin (N2B-us), and a force-dependent interaction between (N2B-us) and the protein FHL2.
- Yuze Sun
- , Xuyao Liu
- & Jie Yan
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Article
| Open AccessA conserved Pol II elongator SPT6L mediates Pol V transcription to regulate RNA-directed DNA methylation in Arabidopsis
How to facilitate the transcription of plant-specific RNA Pol V is largely unknown. Liu et al. find that a conserved RNA Pol II elongator, SPT6L, mediates DNA methylation by its association with Pol V and promoting the production of scaffold RNA.
- Yujuan Liu
- , Jie Shu
- & Chen Chen
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Article
| Open AccessHDAC activity is dispensable for repression of cell-cycle genes by DREAM and E2F:RB complexes
Here, the authors investigate the interplay among DREAM, RB, SIN3 proteins, and HDACs in the context of cell-cycle gene repression, suggesting that E2F:RB and DREAM complexes can repress cell-cycle genes without relying on HDAC activity.
- Alison K. Barrett
- , Manisha R. Shingare
- & Gerd A. Müller
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Article
| Open AccessEnvironment modulates protein heterogeneity through transcriptional and translational stop codon readthrough
This study unveils that stop codon readthrough is prevalent in E. coli, particularly under stress conditions. It highlights the influence of stop codon type and genetic context, with both transcriptional and translational origins.
- Maria Luisa Romero Romero
- , Jonas Poehls
- & Agnes Toth-Petroczy
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Article
| Open AccessH2AX promotes replication fork degradation and chemosensitivity in BRCA-deficient tumours
Histone H2AX has a known role in DNA damage repair but interestingly, its loss is associated with resistance to poly(ADP-ribose) polymerase (PARP) inhibition in BRCA-deficient tumours. Here, the authors identify a role of γH2AX in the degradation of replication forks and demonstrate that H2AX loss drives PARP inhibitor resistance via increased stressed fork stability in BRCA-deficient tumours.
- Diego Dibitetto
- , Martin Liptay
- & Sven Rottenberg
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Article
| Open AccessAngle between DNA linker and nucleosome core particle regulates array compaction revealed by individual-particle cryo-electron tomography
Here, using cryo-ET, the 3D structures of individual nucleosome particles were characterized to observe changes under varying ionic strengths and in the presence of protein H1, revealing key regulatory roles in chromatin organization dynamics.
- Meng Zhang
- , César Díaz-Celis
- & Gang Ren
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Article
| Open AccessTranslation initiation factor eIF1.2 promotes Toxoplasma stage conversion by regulating levels of key differentiation factors
Wang et al. show that Toxoplasma gondii translation initiation factor eIF1.2 is critical for acute to chronic stage transition during infection, underscoring the importance of protein translation in controlling stage differentiation.
- Fengrong Wang
- , Michael J. Holmes
- & Vern B. Carruthers
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Article
| Open AccessDNA methylation-based high-resolution mapping of long-distance chromosomal interactions in nucleosome-depleted regions
Here, the authors present MTAC, a method to map chromosomal interactions in budding yeast. By applying MTAC to various viewpoints, they find that most of the long-distance chromosomal interactions detected by MTAC reflect tethering by the nuclear pore complexes.
- Yi Li
- , James Lee
- & Lu Bai
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Article
| Open AccessDeterminants of gastric cancer immune escape identified from non-coding immune-landscape quantitative trait loci
The role of non-coding mutations in cancer progression and immune evasion needs to be further explored. Here, the authors investigate the potential of common somatic and germline 3′ untranslated region variants in predicting response to immunotherapy in gastric patients.
- Christos Miliotis
- , Yuling Ma
- & Ioannis S. Vlachos
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Article
| Open AccessParental experiences orchestrate locust egg hatching synchrony by regulating nuclear export of precursor miRNA
The parental experience exerts a profound impact on offspring phenotypes. Zhu et al. find that in locusts the population density of parents regulates the hatching synchrony of progeny eggs via the FOXN1-PTBP1/XPO5 pathway, facilitating the nuclear export of precursor miRNA in the oocytes.
- Ya′nan Zhu
- , Jing He
- & Le Kang
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Article
| Open AccessOsMAPK6 phosphorylation and CLG1 ubiquitylation of GW6a non-additively enhance rice grain size through stabilization of the substrate
OsMAPK6 and CLG1, respectively, target GW6a for phosphorylation and ubiquitylation to favor the substrate stabilization using a different mechanism from prior reports, and the corresponding genetic axes operate non-additively to regulate seed size.
- Chen Bai
- , Gao-Jie Wang
- & Xian-Jun Song
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Article
| Open AccessMultiregional transcriptomics identifies congruent consensus subtypes with prognostic value beyond tumor heterogeneity of colorectal cancer
Intratumoral heterogeneity has been documented in multiple cancer types, and can be linked to treatment resistance. Here, the authors analyse multiregional samples from colorectal cancers and show gene expression subtypes which are less vulnerable to heterogeneity and may partly contribute to differential patient survival.
- Jonas Langerud
- , Ina A. Eilertsen
- & Anita Sveen
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Article
| Open AccessBRCA1/BARD1 ubiquitinates PCNA in unperturbed conditions to promote continuous DNA synthesis
Here the authors identify PCNA, a master regulator of DNA replication, as a ubiquitin substrate for the BRCA1/BARD1 heterodimer. This modification is crucial to avoid the appearance of unreplicated DNA gaps in the genome after replication.
- Daniel Salas-Lloret
- , Néstor García-Rodríguez
- & Román González-Prieto
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Article
| Open AccessMitoribosome structure with cofactors and modifications reveals mechanism of ligand binding and interactions with L1 stalk
This study uses cryo-EM, biochemical, and computational approaches to shed light on the fundamental mechanisms underlying the human mitoribosome function, including ligand binding, modifications, Fe-S clusters, and aging-related polyamines.
- Vivek Singh
- , Yuzuru Itoh
- & Alexey Amunts
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Article
| Open AccessSOS1 tonoplast neo-localization and the RGG protein SALTY are important in the extreme salinity tolerance of Salicornia bigelovii
The authors show that in the halophyte Salicornia the sodium transporter SOS1 localizes to the tonoplast, likely storing sodium in the vacuole. The intrinsically disordered protein SALTY, increases yeast salt tolerance possibly stabilizing ribosomes in the ER.
- Octavio R. Salazar
- , Ke Chen
- & Sandra M. Schmöckel
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Article
| Open AccessHomozygous EPRS1 missense variant causing hypomyelinating leukodystrophy-15 alters variant-distal mRNA m6A site accessibility
Here the authors show that a homozygous EPRS1 missense variant causing hypomyelinating leukodystrophy-15 alters the accessibility of variant-distal methylation sites in EPRS1 mRNA, revealing a new RNA-dependent mechanism by which genetic variants can influence gene expression and disease.
- Debjit Khan
- , Iyappan Ramachandiran
- & Paul L. Fox
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Article
| Open AccessExon-junction complex association with stalled ribosomes and slow translation-independent disassembly
Bensaude et al. use a split luciferase approach to show that exon-junction complex assembly and disassembly occur faster when they are translation-dependent than when they are translation-independent; and they uncover an association with ribosomes.
- Olivier Bensaude
- , Isabelle Barbosa
- & Hervé Le Hir
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Article
| Open AccessHigh-throughput mechanical phenotyping and transcriptomics of single cells
The molecular system regulating cell surface mechanics remains largely unexplored at single-cell resolution. Here, the authors report a high-throughput single-cell assay, ELASTomics, which integrates mechanical phenotyping with unbiased transcriptomics.
- Akifumi Shiomi
- , Taikopaul Kaneko
- & Hirofumi Shintaku
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Article
| Open AccessThe nucleic acid binding protein SFPQ represses EBV lytic reactivation by promoting histone H1 expression
Here, Murray-Nerger et al use a genome-wide CRISPR/Cas9 screen to show that the nuclear protein SFPQ suppresses lytic reactivation of Epstein-Barr virus by promoting the expression and accumulation of linker histone H1 on the viral genome.
- Laura A. Murray-Nerger
- , Clarisel Lozano
- & Benjamin E. Gewurz
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Article
| Open AccessBone marrow stromal cells induce chromatin remodeling in multiple myeloma cells leading to transcriptional changes
Bone marrow stromal cells (BMSCs) are known to promote the development of drug resistance. Here, the authors investigate the chromatin remodeling and associated changes in gene expression in the multiple myeloma (MM) cells following their interactions with BMSCs, which are also observed in extramedullary disease (EMD).
- Moritz Binder
- , Raphael E. Szalat
- & Nikhil C. Munshi
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Article
| Open AccessSequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity
Here, the authors show that GalNAc-T3 and T7 regulate furin cleavage of the SARS-CoV-2 spike protein via O-glycosylation. This influences viral assembly and infection, highlighting glycosylation as a host defense mechanism.
- Shengjun Wang
- , Wei Ran
- & Yang Mao
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Article
| Open AccessSevere drought exposure in utero associates to children’s epigenetic age acceleration in a global climate change hot spot
The study suggests a positive association between in utero drought exposure and faster biological aging in children in a global climate change hot spot. Drought experienced during pregnancy may reduce life expectancy.
- Xi Qiao
- , Bilinda Straight
- & Belinda L. Needham
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Article
| Open AccessPost-translational modification-dependent oligomerization switch in regulation of global transcription and DNA damage repair during genotoxic stress
Here the authors show that the human transcription elongation factor AF9, part of Super Elongation Complex (SEC), undergoes oligomerization which can be reverted by post-translational modification in regulation of global transcription.
- Prathama Talukdar
- , Sujay Pal
- & Debabrata Biswas
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Article
| Open AccessNuclear actin structure regulates chromatin accessibility
Intranuclear actin contributes to nuclear structure. Inducing actin remodeling within the nucleus regulates chromatin accessibility, and is associated with phenotypic outcomes in mesenchymal stem cells. As such, dynamic actin remodeling may modulate gene expression.
- Buer Sen
- , Zhihui Xie
- & Janet Rubin
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Article
| Open AccessStructures of H5N1 influenza polymerase with ANP32B reveal mechanisms of genome replication and host adaptation
The authors demonstrate how avian H5N1 influenza A virus polymerase interacts with human ANP32B to facilitate the replication of the viral genetic information in mammalian hosts, revealing insights into cross-species transmission.
- Ecco Staller
- , Loïc Carrique
- & Ervin Fodor
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Article
| Open AccessQuantifying 3′UTR length from scRNA-seq data reveals changes independent of gene expression
While gene expression analysis is commonly performed, 3′UTR length analysis is limited due to technical challenges. Here the authors provide an open-access analysis pipeline for scRNA-seq data to simultaneously quantify gene expression and 3′UTR length.
- Mervin M. Fansler
- , Sibylle Mitschka
- & Christine Mayr
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Article
| Open AccessTranscription stress at telomeres leads to cytosolic DNA release and paracrine senescence
Cellular senescence and the process of transcription are intimately linked, yet the mechanisms involved remain unclear. Here the authors show that a defect in TFIIS leads to telomere dysfunction, genome instability and the release of vesicles that induce senescence to neighboring cells.
- Athanasios Siametis
- , Kalliopi Stratigi
- & George A. Garinis
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Article
| Open AccessGRouNdGAN: GRN-guided simulation of single-cell RNA-seq data using causal generative adversarial networks
Benchmarking GRN inference methods remains a challenge. Here, authors present GRouNdGAN, a causal generative model that imposes a user-defined GRN in its architecture to simulate realistic single-cell data, bridging the gap between synthetic and biological data benchmarks of GRN inference methods.
- Yazdan Zinati
- , Abdulrahman Takiddeen
- & Amin Emad
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Article
| Open AccessTransfer learning enables identification of multiple types of RNA modifications using nanopore direct RNA sequencing
Simultaneous profiling of multiple RNA modifications is a promising yet understudied field of research. Here, authors develop a transferable deep learning framework capable of detecting multiple types of RNA modifications in single nanopore sequencing sample.
- You Wu
- , Wenna Shao
- & Xiang Yu
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Article
| Open AccessdsRNAi-mediated silencing of PIAS2beta specifically kills anaplastic carcinomas by mitotic catastrophe
Anaplastic thyroid cancer (ATC) is a particularly aggressive cancer type with limited effective therapeutic options. Here, the authors identify the SUMO E3 ligase PIAS2 as a potential therapeutic target in ATC and mechanistically investigate its role in mitotic spindle and centrosome assembly.
- Joana S. Rodrigues
- , Miguel Chenlo
- & Clara V. Alvarez
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Article
| Open AccessmTORC1 regulates cell survival under glucose starvation through 4EBP1/2-mediated translational reprogramming of fatty acid metabolism
How cells adapt to glucose starvation is still elusive. Here, Levy et al. show that the mTOR substrate 4EBP1 protects human, mouse, and yeast cells from glucose starvation and is exploited by cancer cells to promote tumorigenesis.
- Tal Levy
- , Kai Voeltzke
- & Gabriel Leprivier
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Article
| Open AccessDeep mutational scanning reveals a correlation between degradation and toxicity of thousands of aspartoacylase variants
The details of how the protein folding and degradation systems collaborate to combat potentially toxic non-native proteins are unknown. Here the authors perform systematic studies of missense and nonsense variants of the cytosolic aspartoacylase, ASPA, where loss-of-function variants are linked to Canavan disease.
- Martin Grønbæk-Thygesen
- , Vasileios Voutsinos
- & Rasmus Hartmann-Petersen
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Article
| Open AccessMethylation of ESCRT-III components regulates the timing of cytokinetic abscission
Methylation of CHMP2B regulates abscission timing by modulating ESCRT-III dynamics during cytokinesis. This methylation also plays a role in HIV-1 budding, highlighting the broader significance of ESCRT-III methylation.
- Aurélie Richard
- , Jérémy Berthelet
- & Souhila Medjkane
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Article
| Open AccessMultiscale modelling of chromatin 4D organization in SARS-CoV-2 infected cells
In this work, the authors apply polymer models to reconstruct the 3D structure of the genome during SARS-CoV-2 infection and examine how the virus impacts key mechanisms of chromatin organization.
- Andrea M. Chiariello
- , Alex Abraham
- & Mario Nicodemi
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Article
| Open AccessMultimodal binding and inhibition of bacterial ribosomes by the antimicrobial peptides Api137 and Api88
Proline-rich antimicrobial peptides (PrAMPs) inhibit bacterial protein biosynthesis. Here, the authors show that the honey-bee derived PrAMPs Api137 and Api88 inhibit bacterial ribosomes through multiple mechanisms, promising for drug development.
- Simon M. Lauer
- , Maren Reepmeyer
- & Ralf Hoffmann
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Article
| Open AccessA nascent riboswitch helix orchestrates robust transcriptional regulation through signal integration
Here the authors unveil an intermediate state during the folding of the manganese riboswitch from L. lactis. This transient state allows the integration of multiple cellular signals including RNA polymerase pausing and transcription factor NusA.
- Adrien Chauvier
- , Shiba S. Dandpat
- & Nils G. Walter
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Article
| Open AccessUnveiling the A-to-I mRNA editing machinery and its regulation and evolution in fungi
A-to-I editing in animals is catalyzed by enzymes of the Adenosine Deaminase Acting on RNA family, orthologues of which do not exist in fungi. Here, Feng et al. characterise the enzymes involved in A-to-I mRNA editing in Fusarium graminearum.
- Chanjing Feng
- , Kaiyun Xin
- & Huiquan Liu
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Article
| Open AccessThree concurrent mechanisms generate gene copy number variation and transient antibiotic heteroresistance
Bacterial heteroresistance is a medically relevant phenotype where small antibiotic-resistant subpopulations coexist within predominantly susceptible bacterial populations. Here, Nicoloff et al. describe how three different mechanisms that increase the copy number of resistance genes can lead to unstable and transient heteroresistance.
- Hervé Nicoloff
- , Karin Hjort
- & Helen Wang
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Article
| Open AccessPrediction of m6A and m5C at single-molecule resolution reveals a transcriptome-wide co-occurrence of RNA modifications
The epitranscriptome holds many unexplored RNA functions, but detecting multiple modifications from one sample remains challenging. Here, authors devise a strategy combining AI and nanopore sequencing to uncover a transcriptome-wide co-occurrence of two modification types in individual RNA molecules.
- P Acera Mateos
- , A J Sethi
- & E Eyras
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Article
| Open AccessA common polymorphism in the Intelectin-1 gene influences mucus plugging in severe asthma
Type 2 inflammation drives the formation of pathologic mucus in patients with asthma. Here, authors reveal a role for intelectin-1 in IL-13-induced mucus properties, and that an ITLN1 eQTL is associated with protection from the formation of mucus plugs in T2-high asthma.
- Jamie L. Everman
- , Satria P. Sajuthi
- & Max A. Seibold
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Article
| Open AccessIdentification and characterization of small molecule inhibitors of the LINE-1 retrotransposon endonuclease
The LINE-1 retrotransposon is a target for the development of therapies to treat age-associated disease. Here the AUs describes the characterization of small molecule inhibitors of the endonuclease domain of LINE-1.
- Alexandra M. D’Ordine
- , Gerwald Jogl
- & John M. Sedivy
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Article
| Open AccessMeCP2 binds to methylated DNA independently of phase separation and heterochromatin organisation
The heterochromatic 'condensates' may not be conserved across mammals. This study highlights the influence of host genome on nuclear architecture and challenges the hypothesis that heterochromatin and MeCP2 undergo phase separation.
- Raphaël Pantier
- , Megan Brown
- & Adrian Bird
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Article
| Open AccessThe miR-144/Hmgn2 regulatory axis orchestrates chromatin organization during erythropoiesis
Differentiation of stem and progenitor cells is a highly regulated process. Here, the authors uncover miR-144 and its target Hmgn2 as the backbone of the genetic regulatory circuit that controls the terminal differentiation of erythrocytes in vertebrates.
- Dmitry A. Kretov
- , Leighton Folkes
- & Daniel Cifuentes
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Article
| Open AccessSpatially revealed roles for lncRNAs in Drosophila spermatogenesis, Y chromosome function and evolution
In Drosophila, long noncoding RNAs (lncRNAs) are expressed most highly in male germline cells. Here the authors report the subcellular distributions of approximately 600 Drosophila lncRNAs in male reproductive tissues, indicating potential involvement in spermatogenesis, fertility and evolution.
- Zhantao Shao
- , Jack Hu
- & Henry M. Krause
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Article
| Open AccessCRISPR-dCas13d-based deep screening of proximal and distal splicing-regulatory elements
Here the authors develop Splice-RUSH, a high-throughput screening method to map both proximal and distal splicing-regulatory sequences in a native sequence context. These sequences can also be targeted by ASOs to modulate splicing.
- Yocelyn Recinos
- , Dmytro Ustianenko
- & Chaolin Zhang
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Article
| Open AccessAllosteric regulation by c-di-AMP modulates a complete N-acetylglucosamine signaling cascade in Saccharopolyspora erythraea
c-di-AMP is essential for bacterial signaling. Here, the authors identify the GlcNAc-sensing regulator DasR as a c-di-AMP receptor and provide molecular insight into their signaling effect on the developmental and antibiotic biosynthesis control across Actinobacteria.
- Di You
- , Liu-Chang Zhao
- & Bang-Ce Ye
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Article
| Open AccessA conserved N-terminal motif of CUL3 contributes to assembly and E3 ligase activity of CRL3KLHL22
The assembly integrity of dimeric CRL3 E3 ligases are important in various physiological and pathological processes. Here, the authors show that an evolutionarily conserved CUL3 N-terminal motif contributes to both the assembly and activity of dimeric CRL3 E3 ligases.
- Weize Wang
- , Ling Liang
- & Yuxin Yin
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Article
| Open AccessDisentangling genetic effects on transcriptional and post-transcriptional gene regulation through integrating exon and intron expression QTLs
Expression quantitative trait loci (eQTL) studies typically only consider exon expression levels and discard intronic RNA sequencing reads. Here, the authors show that analyzing eQTLs together with QTLs for intron levels and exon-intron ratios expands the number and functional understanding of genetic effects on gene regulatory processes.
- Anneke Brümmer
- & Sven Bergmann
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