Integrated Genomic Analysis Reveals Key Features of Long Undecoded Transcript Isoform-based Gene Repression

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2021 Apr 7

PMID 33826921

Citations 16

Authors

Amy Tresenrider

Kaitlin Morse

Victoria Jorgensen

Minghao Chia

Hanna Liao

Folkert Jacobus van Werven

Elcin Unal

Affiliations

Soon will be listed here.

Abstract

Long undecoded transcript isoforms (LUTIs) represent a class of non-canonical mRNAs that downregulate gene expression through the combined act of transcriptional and translational repression. While single gene studies revealed important aspects of LUTI-based repression, how these features affect gene regulation on a global scale is unknown. Using transcript leader and direct RNA sequencing, here, we identify 74 LUTI candidates that are specifically induced in meiotic prophase. Translational repression of these candidates appears to be ubiquitous and is dependent on upstream open reading frames. However, LUTI-based transcriptional repression is variable. In only 50% of the cases, LUTI transcription causes downregulation of the protein-coding transcript isoform. Higher LUTI expression, enrichment of histone 3 lysine 36 trimethylation, and changes in nucleosome position are the strongest predictors of LUTI-based transcriptional repression. We conclude that LUTIs downregulate gene expression in a manner that integrates translational repression, chromatin state changes, and the magnitude of LUTI expression.

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