A potential role for initiator-tRNA in pre-mRNA splicing regulation

Eyal Kamhi, Oleg Raitskin, Ruth Sperling, Joseph Sperling*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

The translation initiator-tRNA plays a crucial role in the initiation of protein synthesis in both prokaryotic and eukaryotic cells, by employing specific base pairing between its anticodon triplet CAU and the general initiation codon AUG in the mRNA. Here we show that the initiator-tRNA may also act, in a manner that is independent of its role in protein translation, as a pre-mRNA splicing regulator. Specifically, we show that alternative splicing events that are induced by mutations in the translation initiation AUG codon can be suppressed by expressing initiator-tRNA constructs carrying anticodon mutations that compensate for the AUG mutations. These mutated initiator-tRNAs appeared to be uncharged with an amino acid. Our results imply that recognition of the initiation AUG sequence by the anticodon triplet of initiator-tRNA in its unloaded state plays a role in quality control of splicing in the cell nucleus by a yet unresolved mechanism. Identifying the initiatort-RNA as a transacting splicing regulator suggests a novel involvement of this molecule in splicing regulation and provides a critical step toward deciphering this intriguing mechanism.

Original languageEnglish
Pages (from-to)11319-11324
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number25
DOIs
StatePublished - 22 Jun 2010

Keywords

  • 5′ splice site
  • Alternative splicing
  • Premature termination codon
  • Spliceosome
  • Suppression of splicing

Fingerprint

Dive into the research topics of 'A potential role for initiator-tRNA in pre-mRNA splicing regulation'. Together they form a unique fingerprint.

Cite this