Intron retention as a new pre-symptomatic marker of aging and its recovery to the normal state by a traditional Japanese multi-herbal medicine

Abstract

Intron retention as a new marker of the pre-disease state and its recovery to the 1 normal state by a traditional Japanese multi-herbal medicine 2 3 Running title: Recovery of alternative splicing from the senescence to healthy type by 4 an herbal medicine 5 6 7

Dysregulated RNA processing and metabolism: a new hallmark of ageing and provocation for cellular senescence

“…Increase in transcriptional noise and production of isoforms with altered functionality [73,74] Disruption to RNA surveillance Failure of RNA quality control and fine tuning of gene expression [77,115] Altered dynamics of RNA turnover Enhanced stability of SASP mRNAs [81,82] Defective RNA export Altered subcellular localisation of mRNAs, nuclear accumulation and impaired translation of mRNAs [88,116] Compromised telomere maintenance…”

“…Recent evidence has also suggested that dynamic retained intron events occur in senescence and in aged tissues, and were negatively correlated with the expression of their host genes [73]. Accumulation of retained introns has also been described in the pre‐symptomatic stage of ageing in wild‐type mouse models [74]. Aberrant isoforms may have dominant negative properties, altered functional characteristics or misdirected subcellular localisation which may have profound implications for cells, tissues and systems and contribute to ageing and senescence phenotypes.…”

3’UTR-Seq analysis of chicken abdominal adipose tissue reveals widespread intron retention in 3’UTR and provides insight into molecular basis of feed efficiency

“…In addition, Green et al [41] reported a positive association between decreased IR in nuclear-detained mRNA and enhanced expression of regulators of immunocyte transcription and inflammatory response. IR was even proposed as a biomarker for aging and pre-obese state [42,43]. For a long time, 3' UTR introns are viewed as marks for nonfunctional transcripts resulting from genomic noise, mutation, and incorrect splicing [44][45][46].…”