Structure and function of pre-mRNA 5'-end capping quality control and 3'-end processing

Biochemistry. 2014 Apr 1;53(12):1882-98. doi: 10.1021/bi401715v. Epub 2014 Mar 20.

Abstract

Messenger RNA precursors (pre-mRNAs) are produced as the nascent transcripts of RNA polymerase II (Pol II) in eukaryotes and must undergo extensive maturational processing, including 5'-end capping, splicing, and 3'-end cleavage and polyadenylation. This review will summarize the structural and functional information reported over the past few years on the large machinery required for the 3'-end processing of most pre-mRNAs, as well as the distinct machinery for the 3'-end processing of replication-dependent histone pre-mRNAs, which have provided great insights into the proteins and their subcomplexes in these machineries. Structural and biochemical studies have also led to the identification of a new class of enzymes (the DXO family enzymes) with activity toward intermediates of the 5'-end capping pathway. Functional studies demonstrate that these enzymes are part of a novel quality surveillance mechanism for pre-mRNA 5'-end capping. Incompletely capped pre-mRNAs are produced in yeast and human cells, in contrast to the general belief in the field that capping always proceeds to completion, and incomplete capping leads to defects in splicing and 3'-end cleavage in human cells. The DXO family enzymes are required for the detection and degradation of these defective RNAs.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Arabidopsis Proteins / chemistry
  • Arabidopsis Proteins / physiology
  • Cleavage And Polyadenylation Specificity Factor / chemistry
  • Cleavage And Polyadenylation Specificity Factor / physiology
  • Humans
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • RNA Precursors / chemistry*
  • RNA Precursors / physiology*
  • RNA Processing, Post-Transcriptional / physiology*
  • RNA, Messenger / chemistry
  • RNA, Messenger / physiology

Substances

  • Arabidopsis Proteins
  • CPSF30 protein, Arabidopsis
  • Cleavage And Polyadenylation Specificity Factor
  • RNA Precursors
  • RNA, Messenger