Series |

RNA processing and modifications

Technological advances in the past decade or so have revolutionized our understanding of the co-transcriptional and post-transcriptional control of gene expression. It has become clear that the different steps of pre-mRNA processing, from 5' capping to nuclear export, are tightly co-regulated and coordinated with transcription, translation and mRNA decay. Furthermore, recent discoveries and the functional characterization of several chemical modifications in mRNA such as N6-methyladenosine (m6A) and 5-methylcytosine (m5C), which together form the epitranscriptome, have revealed a new layer of regulation of mRNA processing and maturation. The articles in this series discuss different aspects of the biogenesis of mRNAs and other RNA species (including rRNA, tRNA, small RNAs and other non-coding RNAs), the regulation of RNA processing and chemical modification, and how these processes affect human physiology and disease.

Reviews

  • Nature Reviews Molecular Cell Biology | Review Article

    The cleavage of microRNA (miRNA) precursors by Drosha and Dicer and their loading with Argonaute proteins into RNA-induced silencing complexes are key steps in miRNA biogenesis. Recent studies have clarified the mechanisms of action of these molecular machines and discovered non-canonical miRNA biogenesis pathways.

    • Thomas Treiber
    • , Nora Treiber
    •  &  Gunter Meister
  • Nature Reviews Molecular Cell Biology | Review Article

    tRNAs exist as diverse species, including sequence isoforms and nuclease-generated fragments, which are further functionally diversified by base modifications and various protein interactions. Perhaps unsurprisingly, tRNAs are now being implicated in various cellular processes beyond protein synthesis per se, including in stress responses, proliferation, cell fate determination and tumorigenesis.

    • Paul Schimmel
  • 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 Molecular Cell Biology | Opinion

    The chemical modifications and structural features of mRNAs are highly dynamic. Together, they regulate the composition and function of the transcriptome by shaping RNA–protein interactions at different stages of the gene expression process.

    • Cole J.T. Lewis
    • , Tao Pan
    •  &  Auinash Kalsotra

Comments

  • Nature Reviews Molecular Cell Biology | Comment

    Novoa, Mason and Mattick propose to use phage display technology and direct sequencing through nanopores to facilitate systematic interrogation of RNA modifications.

    • Eva Maria Novoa
    • , Christopher E. Mason
    •  &  John S. Mattick