Collection |

mRNA splicing: 40 years on

Pre-mRNA splicing is a fundamental step in mRNA maturation and its discovery in 1977 revolutionized our understanding of gene expression. This collection includes reviews and research articles from across the Nature group of journals to showcase the latest advances in splicing research and the emerging understanding of how splicing regulates gene expression, and through it cell fate, development and physiology. The articles focus on topics that include alternative splicing, the architecture and function of spliceosome complexes, the coordination of splicing with other processes such as transcription and mRNA decay, and splicing-related diseases and therapeutics.


  • Nature Reviews Molecular Cell Biology | Review Article

    Atomic-resolution structures have recently been obtained for the intact spliceosome at different stages of the splicing cycle. These structural data have proved that the spliceosome is a protein-directed metalloribozyme and have increased our understanding of pre-mRNA splicing mechanisms, explaining a large body of existing genetic and biochemical data.

    • Yigong Shi
  • Nature Reviews Molecular Cell Biology | Review Article

    Pre-mRNA splicing occurs on nascent RNA, which is attached to chromatin by RNA polymerase II. Much splicing occurs co-transcriptionally, and the spatial and temporal coordination of the two processes is tightly coordinated with other mRNA-processing events.

    • Lydia Herzel
    • , Diana S. M. Ottoz
    • , Tara Alpert
    •  &  Karla M. Neugebauer
  • Nature Reviews Molecular Cell Biology | Review Article

    Alternative splicing expands the complexity of the proteome by generating multiple transcript isoforms from a single gene. Numerous alternative splicing events occur during cell differentiation and tissue maturation, suggesting that alternative splicing supports proper development. Recent studies shed light on how alternative splicing and its coordination contribute to organ development and tissue homeostasis.

    • Francisco E. Baralle
    •  &  Jimena Giudice
  • Nature Reviews Cancer | Review Article

    This Review discusses the current genetic and functional links between dysregulated and/or mutated RNA splicing factors and cancer, as well as the therapeutic opportunities presented by alterations in alternative splicing in cancer.

    • Heidi Dvinge
    • , Eunhee Kim
    • , Omar Abdel-Wahab
    •  &  Robert K. Bradley
  • Nature Reviews Genetics | Review Article

    Complex and intricate RNA splicing mechanisms are crucial for gene regulation and for maximizing proteomic diversity. This Review discusses how alterations to splicing mechanisms — such as mutations in pre-mRNAs, or mutations and dysregulation of core spliceosome proteins and other RNA-binding proteins — results in diverse molecular consequences and various diseases. Opportunities for therapeutic correction of these defects are also explored.

    • Marina M. Scotti
    •  &  Maurice S. Swanson


  • Nature Structural & Molecular Biology | Article

    Genome-wide analyses of the effects of U1 snRNP inhibition in human cells shows that telescripting suppresses premature cleavage and polyadenylation in long introns to sustain expression of large genes important for cell cycle and development.

    • Jung-Min Oh
    • , Chao Di
    • , Christopher C Venters
    • , Jiannan Guo
    • , Chie Arai
    • , Byung Ran So
    • , Anna Maria Pinto
    • , Zhenxi Zhang
    • , Lili Wan
    • , Ihab Younis
    •  &  Gideon Dreyfuss
  • Nature Cell Biology | Article

    Grelet et al. find that hnRNP E1 release from PNUTS pre-RNA in response to TGFβ generates a lncRNA that acts as competitive sponge for miR-205, promoting epithelial–mesenchymal transition in cancer.

    • Simon Grelet
    • , Laura A. Link
    • , Breege Howley
    • , Clémence Obellianne
    • , Viswanathan Palanisamy
    • , Vamsi K. Gangaraju
    • , J. Alan Diehl
    •  &  Philip H. Howe
  • Nature Medicine | Letter

    An HDR-independent therapeutic genome-editing approach corrected the splice-site mutation in Lama2 in a mouse model of congenital muscular dystrophy type 1A, and may be applied more broadly to correct splice-site mutations associated with other diseases.

    • Dwi U Kemaladewi
    • , Eleonora Maino
    • , Elzbieta Hyatt
    • , Huayun Hou
    • , Maylynn Ding
    • , Kara M Place
    • , Xinyi Zhu
    • , Prabhpreet Bassi
    • , Zahra Baghestani
    • , Amit G Deshwar
    • , Daniele Merico
    • , Hui Y Xiong
    • , Brendan J Frey
    • , Michael D Wilson
    • , Evgueni A Ivakine
    •  &  Ronald D Cohn
  • Nature Communications | Article | open

    In prostate cancer tumour aggressiveness can be related to race. Here, the authors identify an alternative RNA splice variant of PIK3CD as a potential mechanism to explain racial disparities in the incidence and aggressiveness of prostate cancer between African American and European American men.

    • Bi-Dar Wang
    • , Kristin Ceniccola
    • , SuJin Hwang
    • , Ramez Andrawis
    • , Anelia Horvath
    • , Jennifer A. Freedman
    • , Jacqueline Olender
    • , Stefan Knapp
    • , Travers Ching
    • , Lana Garmire
    • , Vyomesh Patel
    • , Mariano A. Garcia-Blanco
    • , Steven R. Patierno
    •  &  Norman H. Lee
  • Nature Communications | Article | open

    After transcription the 3′-end of U6 snRNA is oligo-uridylylated by the terminal uridylyltransferase TUT1. Here the authors present the crystal structure of human TUT1 and give insights into the mechanism of 3′-end uridylylation by the enzyme.

    • Seisuke Yamashita
    • , Yuko Takagi
    • , Takashi Nagaike
    •  &  Kozo Tomita