Distinct Functions of the Cap-Binding Complex in Stimulation of Nuclear mRNA Export

Mol Cell Biol. 2019 Apr 2;39(8):e00540-18. doi: 10.1128/MCB.00540-18. Print 2019 Apr 15.

Abstract

Cap-binding complex (CBC) associates cotranscriptionally with the cap structure at the 5' end of nascent mRNA to protect it from exonucleolytic degradation. Here, we show that CBC promotes the targeting of an mRNA export adaptor, Yra1 (forming transcription export [TREX] complex with THO and Sub2), to the active genes and enhances mRNA export in Saccharomyces cerevisiae Likewise, recruitment of Npl3 (an hnRNP involved in mRNA export via formation of export-competent ribonuclear protein complex [RNP]) to the active genes is facilitated by CBC. Thus, CBC enhances targeting of the export factors and promotes mRNA export. Such function of CBC is not mediated via THO and Sub2 of TREX, cleavage and polyadenylation factors, or Sus1 (that regulates mRNA export via transcription export 2 [TREX-2]). However, CBC promotes splicing of SUS1 mRNA and, consequently, Sus1 protein level and mRNA export via TREX-2. Collectively, our results support the hypothesis that CBC promotes recruitment of Yra1 and Npl3 to the active genes, independently of THO, Sub2, or cleavage and polyadenylation factors, and enhances mRNA export via TREX and RNP, respectively, in addition to its role in facilitating SUS1 mRNA splicing to increase mRNA export through TREX-2, revealing distinct stimulatory functions of CBC in mRNA export.

Keywords: CBC; RNA polymerase II; mRNA export; mRNA processing; transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / genetics
  • Active Transport, Cell Nucleus / physiology
  • Nuclear Cap-Binding Protein Complex / genetics
  • Nuclear Cap-Binding Protein Complex / metabolism*
  • Nuclear Proteins / metabolism
  • RNA Cap-Binding Proteins / metabolism*
  • RNA Splicing
  • RNA Transport / physiology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / metabolism
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription Factors / metabolism
  • Transcription, Genetic / genetics
  • mRNA Cleavage and Polyadenylation Factors / metabolism

Substances

  • NPL3 protein, S cerevisiae
  • Nuclear Cap-Binding Protein Complex
  • Nuclear Proteins
  • RNA Cap-Binding Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins
  • Sus1 protein, S cerevisiae
  • Transcription Factors
  • YRA1 protein, S cerevisiae
  • mRNA Cleavage and Polyadenylation Factors