The Heterochromatin protein 1 is a master regulator in RNA splicing precision deficient in ulcerative colitis

Abstract

Altered RNA maturation and decay have well-documented effects on tissue longevity. Yet, RNA metabolism is poorly investigated in the gut epithelium, a constantly renewing tissue particularly challenged by ageing. We found that inactivation of the epigenetic regulator HP1γ in the mouse gut epithelium results in accelerated ageing associated with both ectopic expression of ribosomal RNAs and accumulation of miss-spliced messenger RNAs. A consequence of the latter is the production of progerin, a spliced product of the LMNA gene associated with the Hutchinson Gilford Syndrome. Production of progerin transcript increased naturally in the mouse ageing gut, in correlation with a reduced HP1γ expression. Thus, progerin is a candidate marker of aging of the gut epithelium, while HP1γ inactivation emerges as a new model for accelerated aging in this tissue.

Defective Integrator activity shapes the transcriptome of patients with multiple sclerosis

“…Thus, CBX5 may also function as a regulator of eRNA production. Aligning with such a function, other HP1 family proteins are known to participate in RNA metabolism; notably, SWI6 is responsible for the degradation of heterochromatic transcripts in yeast (12), and HP1γ (CBX3) influences the regulation of alternative splicing in mammals (13)(14)(15)(16)(17). We therefore wished to re-explore the role of CBX5 in MS in the light of high-depth genome-wide RNA-seq data allowing for detection of rare RNA species such as eRNAs and alternative splice junctions.…”