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LINC00998‐encoded micropeptide SMIM30 promotes the G1/S transition of cell cycle by regulating cytosolic calcium level
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LINC00998‐encoded micropeptide SMIM30 promotes the G1/S transition of cell cycle by regulating cytosolic calcium level
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LINC00998‐encoded micropeptide SMIM30 promotes the G1/S transition of cell cycle by regulating cytosolic calcium level
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Journal Article
LINC00998‐encoded micropeptide SMIM30 promotes the G1/S transition of cell cycle by regulating cytosolic calcium level
2023
Overview
The biological functions of short open reading frame (sORF)‐encoded micropeptides remain largely unknown. Here, we report that LINC00998, a previously annotated lncRNA, was upregulated in multiple cancer types and the sORF on LINC00998 encoded a micropeptide named SMIM30. SMIM30 was localized in the membranes of the endoplasmic reticulum (ER) and mitochondria. Silencing SMIM30 inhibited the proliferation of hepatoma cells in vitro and suppressed the growth of tumor xenografts and N‐nitrosodiethylamine‐induced hepatoma. Overexpression of the 5′UTR‐sORF sequence of LINC00998, encoding wild‐type SMIM30, enhanced tumor cell growth, but this was abolished when a premature stop codon was introduced into the sORF via single‐base deletion. Gain‐ and loss‐of‐function studies revealed that SMIM30 peptide but not LINC00998 reduced cytosolic calcium level, increased CDK4, cyclin E2, phosphorylated‐Rb and E2F1, and promoted the G1/S phase transition and cell proliferation. The effect of SMIM30 silencing was attenuated by a calcium chelator or the agonist of sarco/endoplasmic reticulum calcium ATPase (SERCA) pump. These findings suggest a novel function of micropeptide SMIM30 in promoting G1/S transition and cell proliferation by enhancing SERCA activity and reducing cytosolic calcium level.
LINC00998, a previously annotated lncRNA, encodes an ER‐localized micropeptide named SMIM30. The authors found that the peptide, but not the lncRNA, reduced cytosolic calcium level by enhancing SERCA activity, then increased CDK4, cyclin E2 and E2F1 levels, and consequently promoted the G1/S phase transition and cell proliferation. These data unravel a new function of SMIM30 in regulating cytosolic calcium and G1/S transition.
