Year: 2026
Type: article
Abstract: Increased abundance of the nuclear long noncoding RNA (lncRNA) Malat1 drives metastatic progression and is a strong predictor of poor patient prognosis. Although the mechanism that stabilizes Malat1 through processing of its 3' terminus is well-characterized, the pathways governing its turnover remain poorly understood. Here, we show that upon exit from mitosis, Malat1 localizes to the cytoplasm, where it is degraded during early G1, resetting its abundance at the start of each cell cycle. Mechanistically, we demonstrate that Malat1 turnover is mediated by a translation- and Smg1-dependent decay pathway and triggered by redundant elements. Importantly, failure to reset Malat1 levels in early G1, due to decay inhibition or in the absence of progression through mitosis, results in Malat1 accumulation. These findings uncover a cell cycle-dependent mechanism that harnesses the translation machinery to regulate Malat1 abundance and identify cancer cell dormancy as a potential mechanism underlying the widespread overexpression of Malat1 in cancer.
Source: The Journal of Cell Biology
Institution: Yale University
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W7204174587