The pioneer round of translation ensures proper targeting of ER and mitochondrial proteins

Joori Park, Jeeyoon Chang, Hyun Jung Hwang, Kwon Jeong, Hyuk Joon Lee, Hongseok Ha, Yeonkyoung Park, Chunghun Lim, Jae Sung Woo, Yoon Ki Kim

Research output: Contribution to journalArticlepeer-review

Abstract

The pioneer (or first) round of translation of newly synthesized mRNAs is largely mediated by a nuclear cap-binding complex (CBC). In a transcriptome-wide analysis of polysome-associated and CBC-bound transcripts, we identify RN7SL1, a noncoding RNA component of a signal recognition particle (SRP), as an interaction partner of the CBC. The direct CBC-SRP interaction safeguards against abnormal expression of polypeptides from a ribosome-nascent chain complex (RNC)-SRP complex until the latter is properly delivered to the endoplasmic reticulum. Failure of this surveillance causes abnormal expression of misfolded proteins at inappropriate intracellular locations, leading to a cytosolic stress response. This surveillance pathway also blocks protein synthesis through RNC-SRP misassembled on an mRNA encoding a mitochondrial protein. Thus, our results reveal a surveillance pathway in which pioneer translation ensures proper targeting of endoplasmic reticulum and mitochondrial proteins.

Original languageEnglish
Pages (from-to)12517-12534
Number of pages18
JournalNucleic acids research
Volume49
Issue number21
DOIs
Publication statusPublished - 2021 Dec 2

ASJC Scopus subject areas

  • Genetics

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