Rna metabolism

Letter | 15 May 2013

Structure-guided discovery of the metabolite carboxy-SAM that modulates tRNA function

Members of the SAM-dependent methyltransferase superfamily are involved in the modification of wobble uridine to 5-oxacetyl uridine in Gram-negative bacteria; CmoA converts SAM to carboxy-SAM (Cx-SAM; a metabolite that was unknown previously), and CmoB uses Cx-SAM to convert 5-hydroxyuridine to 5-oxyacetyl uridine in tRNA.

Jungwook Kim
, Hui Xiao
& Steven C. Almo

Letter | 17 April 2013

A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28–let-7 pathway

This study shows that Dis3l2 is the 3′–5′ exonuclease that mediates the degradation of uridylated precursor let-7 microRNA; this is the first physiological RNA substrate identified for this new exonuclease, which causes the Perlman syndrome of fetal overgrowth and Wilms’ tumour susceptibility when mutated.

Hao-Ming Chang
, Robinson Triboulet
& Richard I. Gregory

Letter | 24 February 2013

CPEB1 coordinates alternative 3′-UTR formation with translational regulation

CPEB1 is known to regulate cytoplasmic polyadenylation, and is now shown to have a second function in the nucleus; it associates with the cleavage and polyadenylation machinery, thereby promoting usage of an upstream poly(A) signal in many messenger RNAs, and affecting alternative splicing.

Felice-Alessio Bava
, Carolina Eliscovich
& Raúl Méndez

Letter | 23 December 2012

Identification of small RNA pathway genes using patterns of phylogenetic conservation and divergence

To identify comprehensively factors involved in RNAi and microRNA-mediated gene expression regulation, this study performed a phylogenetic analysis of 86 eukaryotic species; the candidates this approach highlighted were subjected to Bayesian analysis with transcriptional and proteomic interaction data, identifying protein orthologues of already known RNAi silencing factors, as well as other hits involved in splicing, suggesting a connection between the two processes.

Yuval Tabach
, Allison C. Billi
& Gary Ruvkun

Article | 12 December 2012

FMRP targets distinct mRNA sequence elements to regulate protein expression

RNA-recognition elements are identified for the fragile-X-syndrome-associated RNA-binding protein FMRP, in addition to its target messenger RNAs; although many of FMRP gene targets discovered are involved in brain function and autism spectrum disorder, a proportion are also dysregulated in mouse ovaries, suggesting cross-regulation of signalling pathways in different tissues.

Manuel Ascano
, Neelanjan Mukherjee
& Thomas Tuschl

Letter | 02 September 2012

Structural basis for RNA-duplex recognition and unwinding by the DEAD-box helicase Mss116p

Analysis of the yeast DEAD-box nucleic acid helicase Mss116p provides a structural model for how DEAD-box proteins recognize and unwind RNA duplexes.

Anna L. Mallam
, Mark Del Campo
& Alan M. Lambowitz

Letter | 23 May 2012

Cryptic peroxisomal targeting via alternative splicing and stop codon read-through in fungi

Translocation of glycolytic enzymes to peroxisomes in fungi suggests broader metabolic role for this organelle.

Johannes Freitag
, Julia Ast
& Michael Bölker

Article | 29 April 2012

Topology of the human and mouse m⁶A RNA methylomes revealed by m⁶A-seq

N⁶-methyladenosine (m⁶A) is the most prevalent internal modification in messenger RNA; here the human and mouse m⁶A modification landscape is presented in a transcriptome-wide manner, providing insights into this epigenetic modification.

Dan Dominissini
, Sharon Moshitch-Moshkovitz
& Gideon Rechavi

Letter | 25 March 2012

DBIRD complex integrates alternative mRNA splicing with RNA polymerase II transcript elongation

Characterization of the human interactome of chromatin-associated messenger ribonucleoprotein particles identifies DBC1 and a new protein (ZIRD) as subunits of a protein complex (DBIRD) that binds directly to RNAPII, regulates alternative splicing of exons embedded in (A + T)-rich DNA, and whose depletion results in region-specific decreases in transcript elongation.

Pierre Close
, Philip East
& Jesper Q. Svejstrup

News | 15 March 2012

RNA editing study under intense scrutiny

Debate highlights pitfalls in interpreting genomic data.

Erika Check Hayden

Article | 03 November 2011

CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing

Sanjeev Shukla
, Ersen Kavak
& Shalini Oberdoerffer

News & Views | 05 October 2011

A hidden ancestral legacy trumped

A previously unsuspected genetic mechanism underlies a type of muscular dystrophy common in Japan. A therapeutic approach based on this finding and tested in mice has come up with encouraging results. See Letter p.127

Masayuki Nakamori
& Charles Thornton

Letter | 05 October 2011

Pathogenic exon-trapping by SVA retrotransposon and rescue in Fukuyama muscular dystrophy

Mariko Taniguchi-Ikeda
, Kazuhiro Kobayashi
& Tatsushi Toda

Letter | 03 August 2011

Ganglion-specific splicing of TRPV1 underlies infrared sensation in vampire bats

Elena O. Gracheva
, Julio F. Cordero-Morales
& David Julius

Article | 13 July 2011

Dicer recognizes the 5′ end of RNA for efficient and accurate processing

Jong-Eun Park
, Inha Heo
& V. Narry Kim

Letter | 13 July 2011

Multi-domain conformational selection underlies pre-mRNA splicing regulation by U2AF

Cameron D. Mackereth
, Tobias Madl
& Michael Sattler

Letter | 15 June 2011

Converting nonsense codons into sense codons by targeted pseudouridylation

John Karijolich
& Yi-Tao Yu

News | 25 May 2011

Evidence of altered RNA stirs debate

Sceptics question find that upends biology's 'central dogma'.

Erika Check Hayden

Article | 25 May 2011

Role of the ubiquitin-like protein Hub1 in splice-site usage and alternative splicing

Shravan Kumar Mishra
, Tim Ammon
& Stefan Jentsch

News | 19 May 2011

Cells may stray from 'central dogma'

The ability to edit RNA to produce 'new' protein-coding sequences could be widespread in human cells.

Erika Check Hayden

Letter | 24 April 2011

Structure of the spliceosomal U4 snRNP core domain and its implication for snRNP biogenesis

Adelaine K. W. Leung
, Kiyoshi Nagai
& Jade Li

Article | 30 March 2011

CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III

CRISPR is a microbial RNA-based immune system protecting against viral and plasmid invasions. The CRISPR system is thought to rely on cleavage of a precursor RNA transcript by Cas endonucleases, but not all species possessing CRISPR-type immunity encode Cas proteins. This study now describes an alternative pathway in Streptococcus pyogenes that employs trans-encoded small RNA that directs the processing of precursor RNA into crRNAs through endogenous RNase III and the CRISPR-associated Csn1 protein.

Elitza Deltcheva
, Krzysztof Chylinski
& Emmanuelle Charpentier

Letter | 27 March 2011

A conserved mechanism of DEAD-box ATPase activation by nucleoporins and InsP₆ in mRNA export

Ben Montpetit
, Nathan D. Thomsen
& Karsten Weis

Letter | 09 February 2011

lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3′ UTRs via Alu elements

Staufen 1 (STAU1) protein binds regions of dsRNA in the 3′ UTR of mRNAs and promotes their degradation, a process known as SMD (Staufen-mediated mRNA decay). Although a specific stem-loop binding site had been defined for one SMD target, it was unclear how STAU1 was directed to other SMD targets that lack this structure. This paper reports that pairing of Alu element sequences in long non-coding RNAs (lncRNAs) and in the 3′ UTR of the SMD target generates a dsRNA structure that STAU1 recognizes. This result highlights a new function for lncRNAs.

Chenguang Gong
& Lynne E. Maquat

Research Highlights | 17 November 2010

Epigenetics: What makes a queen bee?

News | 05 November 2010

DNA sequence may be lost in translation

Researchers tackle a mysterious genetic phenomenon

Alla Katsnelson

Letter | 20 October 2010

A methyl transferase links the circadian clock to the regulation of alternative splicing

Various biological processes are entrained by the day–night cycle to occur at a specific time of day. One way the circadian system exerts these effects is through post-transcriptional regulation. These authors show that a protein that transfers methyl groups onto several spliceosome subunits, PRMT5, is regulated by the light–dark cycle. Methylation of these subunits affects alternative splicing of some genes, thus making them subject to circadian control.

Sabrina E. Sanchez
, Ezequiel Petrillo
& Marcelo J. Yanovsky

Article | 13 October 2010

Single-molecule analysis of Mss116-mediated group II intron folding

DEAD-box helicases use ATP hydrolysis to unwind duplex RNA and facilitate RNA or RNA–protein remodelling. One such helicase is Mss116, which targets a particular group II intron in RNA. Here, single-molecule fluorescence was used to monitor the effect of Mss16 on a minimal construct containing this intron. The data show that Mss16 stimulates the sampling of different folded states of the RNA. Moreover, the helicase promotes RNA folding through discrete ATP-independent and ATP-dependent steps.

Krishanthi S. Karunatilaka
, Amanda Solem
& David Rueda

Article | 29 September 2010

U1 snRNP protects pre-mRNAs from premature cleavage and polyadenylation

Splicing is carried out by a collection of protein–RNA complexes known as snRNPs. The spliceosome contains equal quantities of the U1, U2, U4, U5 and U6 snRNPs, but the U1 snRNP is made in levels excess to the amounts needed to form spliceosomes, leading to the idea that excess U1s might have splicing independent functions. Here it is shown that the U1 snRNA interacts with some pre mRNAs whose introns have cryptic polyadenylation sites. This interaction prevents premature termination and polyadenylation of the pre mRNA.

Daisuke Kaida
, Michael G. Berg
& Gideon Dreyfuss

Letter | 29 August 2010

Identification of a quality-control mechanism for mRNA 5′-end capping

Following their synthesis, eukaryotic messenger RNAs have a 7-methylguanosine cap added to their 5′ ends to protect the mRNAs from degradation. Here it is shown that, in vitro and in yeast, caps lacking a methyl group are recognized by the Rai1 protein, which clips off the incomplete cap. The data provide evidence that Rai1 is part of a quality-control mechanism that monitors, and promotes the digestion of, aberrant mRNAs that might arise during stress conditions.

Xinfu Jiao
, Song Xiang
& Megerditch Kiledjian

Article | 06 May 2010

Deciphering the splicing code

The coding capacity of the genome is greatly expanded by the process of alternative splicing, which enables a single gene to produce more than one distinct protein. Can the expression of these different proteins be predicted from sequence data? Here, modelling based on information theory has been used to develop a 'splicing code', which can predict, with good accuracy, tissue-dependent changes in alternative splicing.

Yoseph Barash
, John A. Calarco
& Brendan J. Frey

Letter | 04 February 2010

Multiple native states reveal persistent ruggedness of an RNA folding landscape

The 'thermodynamic hypothesis' proposes that the sequence of a biological macromolecule defines its folded, active structure as a global energy minimum in the folding landscape; however, it is not clear whether there is only one global minimum or several local minima corresponding to active conformations. Here, using single-molecule experiments, an RNA enzyme is shown to fold into multiple distinct native states that interconvert.

Sergey V. Solomatin
, Max Greenfeld
& Daniel Herschlag

Review Article | 27 January 2010

Expansion of the eukaryotic proteome by alternative splicing

Timothy W. Nilsen
& Brenton R. Graveley

RNA metabolism articles within Nature