Chromatin-associated YTHDC1 coordinates heat-induced reprogramming of gene expression

Area of Science:

• Molecular biology
• Epigenetics
• RNA biology

Background:

• Heat stress (HS) profoundly alters cellular gene expression.
• N6-methyladenosine (m6A) is a key RNA modification influencing gene expression.
• YTHDC1 is an m6A reader protein implicated in RNA biology.

Purpose of the Study:

• To investigate the role of human YTHDC1 in the cellular response to heat stress.
• To elucidate how YTHDC1 mediates gene expression reprogramming during heat stress.

Main Methods:

• Chromatin immunoprecipitation (ChIP) to assess YTHDC1 localization.
• RNA sequencing to analyze gene expression and splicing.
• Analysis of YTHDC1 binding to m6A-modified transcripts and non-coding RNAs.

Main Results:

• Heat stress causes YTHDC1 redistribution to chromatin and heat shock protein (HSP) genes.
• YTHDC1 binding to m6A-modified HSP transcripts promotes their expression.
• YTHDC1 regulates intron retention in hundreds of genes during HS.
• YTHDC1 localizes to nuclear stress bodies (nSBs) and binds SATIII non-coding RNAs upon HS.

Conclusions:

• YTHDC1 plays a critical role in m6A-based gene expression reprogramming during heat stress.
• YTHDC1's dynamic localization, including sequestration in nSBs, calibrates the timing of this response.