AI Article Synopsis
- Intestinal stem cells (ISCs) help heal and regenerate the lining of the intestines.
- Researchers found a special type of RNA called circBtnl1 that affects how ISCs heal.
- When the circBtnl1 was removed in mice, it made the ISCs work better and heal faster by increasing a protein called ATF4, which helps with self-renewal.
Article Abstract
Intestinal stem cells (ISCs) at the crypt base are responsible for the regeneration of the intestinal epithelium. However, how ISC self-renewal is regulated still remains unclear. Here we identified a circular RNA, circBtnl1, that is highly expressed in ISCs. Loss of circBtnl1 in mice enhanced ISC self-renewal capacity and epithelial regeneration, without changes in mRNA and protein levels of its parental gene Btnl1. Mechanistically, circBtnl1 and Atf4 mRNA competitively bound the ATP-dependent RNA helicase Ddx3y to impair the stability of Atf4 mRNA in wild-type ISCs. Furthermore, ATF4 activated Sox9 transcription by binding to its promoter via a unique motif, to enhance the self-renewal capacity and epithelial regeneration of ISCs. In contrast, circBtnl1 knockout promoted Atf4 mRNA stability and enhanced ATF4 expression, which caused Sox9 transcription to potentiate ISC stemness. These data indicate that circBtnl1-mediated Atf4 mRNA decay suppresses Sox9 transcription that negatively modulates self-renewal maintenance of ISCs.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10015366 | PMC |
| http://dx.doi.org/10.15252/embj.2022112039 | DOI Listing |
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