AI Article Synopsis
- DMD is a pathway that monitors specific non-coding RNAs, and mutations in the DIS3L2 gene are linked to Perlman syndrome, but the consequences of disrupted DMD are not well understood.
- Ribosome profiling reveals that DIS3L2-deficient cells exhibit specific issues with the translation of mRNAs destined for the endoplasmic reticulum (ER).
- The absence of DIS3L2 leads to problems with the 7SL RNA, affecting ER translation, which results in calcium leakage, activating signaling pathways that disrupt stem cell differentiation.
Article Abstract
DIS3L2-mediated decay (DMD) is a surveillance pathway for certain non-coding RNAs (ncRNAs) including ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), small nuclear RNAs (snRNAs), and RMRP. While mutations in DIS3L2 are associated with Perlman syndrome, the biological significance of impaired DMD is obscure and pathological RNAs have not been identified. Here, by ribosome profiling (Ribo-seq) we find specific dysregulation of endoplasmic reticulum (ER)-targeted mRNA translation in DIS3L2-deficient cells. Mechanistically, DMD functions in the quality control of the 7SL ncRNA component of the signal recognition particle (SRP) required for ER-targeted translation. Upon DIS3L2 loss, sustained 3'-end uridylation of aberrant 7SL RNA impacts ER-targeted translation and causes ER calcium leakage. Consequently, elevated intracellular calcium in DIS3L2-deficient cells activates calcium signaling response genes and perturbs ESC differentiation. Thus, DMD is required to safeguard ER-targeted mRNA translation, intracellular calcium homeostasis, and stem cell differentiation.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250864 | PMC |
| http://dx.doi.org/10.1038/s41467-020-16418-y | DOI Listing |
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