Transcriptional adaptation: where mRNA decay meets genetic compensation

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Current Opinion in Genetics & Development Pub Date : 2025-06-10 DOI:10.1016/j.gde.2025.102369

Lara Falcucci , Brian Juvik , Didier YR Stainier

引用次数: 0

Abstract

Nonsense-mediated mRNA decay (NMD) is a translation-coupled quality control mechanism that safeguards cells against faulty transcripts that could lead to truncated and potentially harmful proteins. However, we posit that there is another side to NMD: it does not just clear away defective transcripts, it also triggers a form of genetic compensation known as transcriptional adaptation (TA). This recently discovered cellular response operates independently of protein loss. Instead, mutant mRNA decay can lead to the upregulation of functional paralogs, thereby compensating for the loss of the mutated gene. Consequently, TA could play a prominent role in genotype-phenotype correlations in human genetic diseases.

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转录适应：mRNA衰变与遗传补偿

无义介导的mRNA衰变（NMD）是一种翻译耦合的质量控制机制，可保护细胞免受可能导致截断和潜在有害蛋白质的错误转录。然而，我们假设NMD还有另一方面：它不仅清除有缺陷的转录本，它还触发一种称为转录适应（TA）的遗传补偿形式。这种最近发现的细胞反应独立于蛋白质损失而起作用。相反，突变的mRNA衰减可以导致功能类似物的上调，从而补偿突变基因的损失。因此，TA可能在人类遗传疾病的基因型-表型相关性中发挥重要作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Opinion in Genetics & Development 生物-细胞生物学

CiteScore

7.90

自引率

0.00%

发文量

102

审稿时长

1 months

期刊介绍： Current Opinion in Genetics and Development aims to stimulate scientifically grounded, interdisciplinary, multi-scale debate and exchange of ideas. It contains polished, concise and timely reviews and opinions, with particular emphasis on those articles published in the past two years. In addition to describing recent trends, the authors are encouraged to give their subjective opinion of the topics discussed. In Current Opinion in Genetics and Development we help the reader by providing in a systematic manner: 1. The views of experts on current advances in their field in a clear and readable form. 2. Evaluations of the most interesting papers, annotated by experts, from the great wealth of original publications.[...] The subject of Genetics and Development is divided into six themed sections, each of which is reviewed once a year: • Cancer Genomics • Genome Architecture and Expression • Molecular and genetic basis of disease • Developmental mechanisms, patterning and evolution • Cell reprogramming, regeneration and repair • Genetics of Human Origin / Evolutionary genetics (alternate years)