The mitochondrial micropeptide Stmp1 promotes retinal cell differentiation

Biochem Biophys Res Commun. 2022 Dec 25;636(Pt 2):79-86. doi: 10.1016/j.bbrc.2022.10.107. Epub 2022 Nov 3.

Abstract

During mammalian retinal development, the differentiation of multipotent progenitors depends on the coordinated action of a variety of intrinsic factors including non-coding RNAs (ncRNAs). To date, many small open reading frames have been identified in ncRNAs to encode micropeptides that function in diverse biological processes; however, it remains unclear whether they have a role in retinal development. Here we report that the 47-amino acid (AA) mitochondrial micropeptide Stmp1 encoded by the lncRNA 1810058I24Rik is involved in retinal differentiation. As the major protein product of 1810058I24Rik, Stmp1 promotes the differentiation of bipolar, amacrine and Müller cells as 1810058I24Rik does when overexpressed in neonatal murine retinas. Moreover, we have identified the 15-AA N-terminus of Stmp1 as its mitochondrion-targeting sequence as well as 5 conserved AA residues that affect protein stability and/or retinal cell differentiation. Together, our data reveal several novel characteristics of Stmp1 and uncover a role for Stmp1 in retinal cell differentiation perhaps through regulating mitochondrial function.

Keywords: Differentiation; Micropeptide; Mitochondria; Retinal development; Stmp1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Ependymoglial Cells / cytology
  • Intracellular Signaling Peptides and Proteins* / physiology
  • Mice
  • Mitochondria* / metabolism
  • Mitochondrial Proteins* / physiology
  • Neurons / cytology
  • RNA, Untranslated / genetics
  • Retina* / cytology

Substances

  • RNA, Untranslated
  • 1810058I24Rik protein, mouse
  • Mitochondrial Proteins
  • Intracellular Signaling Peptides and Proteins