Free Introns of TRNAs As Complementarity-dependent Regulators of Gene Expression

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2025 Feb 12

PMID 39938518

Authors

Regina T Nostramo

Paolo L Sinopoli

Alicia Bao

Sara Metcalf

Lauren M Peltier

Anita K Hopper

Affiliations

Soon will be listed here.

Abstract

From archaea to humans, a subset of transfer RNA (tRNA) genes possesses an intron that must be removed from transcribed pre-tRNAs to generate mature, functional tRNAs. Evolutionary conservation of tRNA intron sequences suggests that tRNA introns perform sequence-dependent cellular functions, which are presently unknown. Here, we demonstrate that free introns of tRNAs (fitRNAs) in Saccharomyces cerevisiae serve as small regulatory RNAs that inhibit mRNA levels via long (13-15 nt) statistically improbable stretches of (near) perfect complementarity to mRNA coding regions. The functions of fitRNAs are both constitutive and inducible because genomic deletion or inducible overexpression of tRNA introns led to corresponding increases or decreases in levels of complementary mRNAs. Remarkably, although tRNA introns are usually rapidly degraded, fitRNA selectively accumulates following oxidative stress, and target mRNA levels decrease. Thus, fitRNAs serve as gene regulators that fine-tune basal mRNA expression and alter the network of mRNAs that respond to oxidative stress.

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