RNA splicing

  • Article
    | Open Access

    The cryo-electron microscopy structure of a newly identified, early spliceosomal complex reveals the mechanism by which the RNA helicase Prp5 enhances the fidelity of the excision of introns from precursor mRNAs.

    • Zhenwei Zhang
    • , Norbert Rigo
    •  & Reinhard Lührmann
  • Article |

    The cryo-EM structure of human U2 small nuclear ribonucleoprotein (snRNP) offers insights into what rearrangements are required for this snRNP to be stably incorporated into the spliceosome, and the role that the DEAD-box ATPase PRP5 may have in these rearrangements.

    • Zhenwei Zhang
    • , Cindy L. Will
    •  & Holger Stark
  • Article |

    Transcriptomic and genetic analyses of a deletion set of all known introns in genes of the budding yeast Saccharomyces cerevisiae indicate that introns promote resistance to starvation.

    • Julie Parenteau
    • , Laurine Maignon
    •  & Sherif Abou Elela
  • Article |

    The cryo-electron microscopy structure of the yeast spliceosome in a pre-catalytic state provides insights into the molecular events leading to formation of the spliceosome active site.

    • Clemens Plaschka
    • , Pei-Chun Lin
    •  & Kiyoshi Nagai
  • Letter |

    The cryo-electron microscopy structure of a yeast spliceosome stalled before mature RNA formation provides insight into the mechanism of exon ligation.

    • Sebastian M. Fica
    • , Chris Oubridge
    •  & Kiyoshi Nagai
  • Letter |

    Gene expression analysis in brain tissue from individuals with and without autism spectrum disorder (ASD) suggests that the transcription factor SOX5 contributes to an ASD-associated reduction in transcriptional differences between brain areas and indicates that common transcriptomic changes occur in different forms of ASD.

    • Neelroop N. Parikshak
    • , Vivek Swarup
    •  & Daniel H. Geschwind
  • Letter |

    The observations that introns are acquired in bursts and that exons are often nucleosome-sized can be explained by the generation of introns from DNA transposons, which insert between nucleosomes.

    • Jason T. Huff
    • , Daniel Zilberman
    •  & Scott W. Roy
  • Article |

    A 3.7 Å resolution structure for the yeast U4/U6.U5 tri-snRNP, a complex involved in splicing, allows a better appreciation of the architecture of the tri-snRNP, and offers new functional insights into the activation of the spliceosome and the assembly of the catalytic core.

    • Thi Hoang Duong Nguyen
    • , Wojciech P. Galej
    •  & Kiyoshi Nagai
  • Letter |

    Splicing factors such as BUD31 are identified in a synthetic-lethal screen with cells overexpressing the transcription factor MYC; oncogenic MYC leads to an increase in pre-mRNA synthesis, and spliceosome inhibition impairs the growth and tumorigenicity of MYC-dependent breast cancers, suggesting that spliceosome components may be potential therapeutic targets for MYC-driven cancers.

    • Tiffany Y.-T. Hsu
    • , Lukas M. Simon
    •  & Thomas F. Westbrook
  • Article |

    Transcription-blocking DNA lesions result in chromatin displacement of core spliceosomes containing U2 and U5 snRNPs; consequently, R-loops containing the nascent transcript are formed, which activate ATM in a feed-forward fashion to influence spliceosome dynamics and alternative splicing.

    • Maria Tresini
    • , Daniël O. Warmerdam
    •  & Jurgen A. Marteijn
  • Article |

    This study determines the structure of the spliceosomal tri-snRNP complex (containing three small nuclear RNAs and more than 30 proteins) by single-particle cryo-electron microscopy; the resolution is sufficient to discern the organization of RNA and protein components involved in spliceosome activation, exon alignment and catalysis.

    • Thi Hoang Duong Nguyen
    • , Wojciech P. Galej
    •  & Kiyoshi Nagai
  • Letter |

    Highly conserved recursive splice sites are identified in vertebrates, particularly within long genes encoding proteins that are involved in neuronal development; analysis of the splicing mechanism reveals that such recursive splicing sites can be used to dictate different mRNA isoforms.

    • Christopher R. Sibley
    • , Warren Emmett
    •  & Jernej Ule
  • Letter |

    In flies, some introns contain internal splice sites that cause ‘recursive splicing’, a multi-step removal of a single intron; this study demonstrates that the scope of this regulatory mechanism is much more extensive in flies than had been appreciated, and provides details about the recursive splicing process.

    • Michael O. Duff
    • , Sara Olson
    •  & Brenton R. Graveley
  • Article |

    This study determines the structure of a branched lariat RNA, providing insights into rearrangement of the intron between the two steps of RNA splicing.

    • Aaron R. Robart
    • , Russell T. Chan
    •  & Navtej Toor
  • Letter |

    CFIm25 is identified as a factor that prevents messenger RNAs being shortened due to altered 3′ polyadenylation, which typically occurs when cells undergo high proliferation and correlates with increased tumorigenic activity in glioblastoma tumours.

    • Chioniso P. Masamha
    • , Zheng Xia
    •  & Eric J. Wagner
  • Article |

    The spliceosome is shown to catalyse splicing through the RNA and not the protein components of the spliceosome; pre-messenger RNA splicing requires U6 snRNA acting by a mechanism similar to that used by group II self-splicing introns.

    • Sebastian M. Fica
    • , Nicole Tuttle
    •  & Joseph A. Piccirilli
  • Letter |

    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 |

    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 |

    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
  • Article |

    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