bims-micpro 2022-05-15 papers

Issue of 2022‒05‒15
four papers selected by
Thomas Farid Martínez
University of California, Irvine

Cancer Lett. 2022 May 06. pii: S0304-3835(22)00207-5. [Epub ahead of print] 215723

Sarra Setrerrahmane, Mengwei Li, Abdelmoumin Zoghbi, Xue Lv, Sen Zhang, Wenjing Zhao, Jingjing Lu, David J Craik, Hanmei Xu.

An exciting emerging topic in the noncoding RNA (ncRNA) field is the discovery of short peptides called micropeptides (≤100 amino acids), whose novel therapeutic opportunities remain under-explored. Micropeptides have been suggested to play essential regulatory roles in diverse species of physiological and pathological processes. Genomics studies have revealed that these micropeptides are encoded by small open reading frames (sORFs) concealed in misannotated ncRNAs, generally lncRNAs (long noncoding RNAs) and circRNAs (circular RNAs). These ncRNA-encoded micropeptides have been shown to contribute to tumorigenesis but little is known about their pathological mechanism because of challenges in translated sORF identification techniques. Here, we review the best-validated micropeptides involved in the progression of human tumors and discuss their therapeutic and/or prognostic potential, at the same time, we also give our own suggestions on the concept of potential-coding RNA and micropeptides.

Keywords: Misannotated ncRNAs; circRNAs; lncRNAs; ncRNA-encoded micropeptides; sORFs

DOI: https://doi.org/10.1016/j.canlet.2022.215723

Acta Biochim Biophys Sin (Shanghai). 2022 Mar 25. 54(3): 292-300

Micropeptides translated from putative long non-coding RNAs.

Junhong Li, Lei Qu, Lingjie Sang, Xinyu Wu, Anlan Jiang, Jian Liu, Aifu Lin.

Long non-coding RNAs (lncRNAs) transcribed in mammals and eukaryotes were thought to have no protein coding capability. However, recent studies have suggested that plenty of lncRNAs are mis-annotated and virtually contain coding sequences which are translated into functional peptides by ribosomal machinery, and these functional peptides are called micropeptides or small peptides. Here we review the rapidly advancing field of micropeptides translated from putative lncRNAs, describe the strategies for their identification, and elucidate their critical roles in many fundamental biological processes. We also discuss the prospects of research in micropeptides and the potential applications of micropeptides.

Keywords: coding-potential; long non-coding RNA (lncRNA); micropeptide; small open reading frame (sORF)

DOI: https://doi.org/10.3724/abbs.2022010

Genome Biol. 2022 May 09. 23(1): 111

Non-AUG translation initiation in mammals.

Dmitry E Andreev, Gary Loughran, Alla D Fedorova, Maria S Mikhaylova, Ivan N Shatsky, Pavel V Baranov.

Recent proteogenomic studies revealed extensive translation outside of annotated protein coding regions, such as non-coding RNAs and untranslated regions of mRNAs. This non-canonical translation is largely due to start codon plurality within the same RNA. This plurality is often due to the failure of some scanning ribosomes to recognize potential start codons leading to initiation downstream-a process termed leaky scanning. Codons other than AUG (non-AUG) are particularly leaky due to their inefficiency. Here we discuss our current understanding of non-AUG initiation. We argue for a near-ubiquitous role of non-AUG initiation in shaping the dynamic composition of mammalian proteomes.

DOI: https://doi.org/10.1186/s13059-022-02674-2

Cancer Res. 2022 May 11. pii: canres.3910.2021. [Epub ahead of print]

Mitochondrial micropeptide STMP1 enhances mitochondrial fission to promote tumor metastasis.

Chen Xie, Feng-Yi Wang, Ye Sang, Bin Chen, Jia-Hui Huang, Feng-Jun He, Hui Li, Ying Zhu, Xingguo Liu, Shi-Mei Zhuang, Jian-Hong Fang.

Micropeptides are a recently discovered class of molecules that play vital roles in various cellular processes, including differentiation, proliferation, and apoptosis. Here, we sought to identify cancer-associated micropeptides and to uncover their mechanistic functions. A micropeptide named short trans-membrane protein 1 (STMP1) that localizes at the inner mitochondrial membrane was identified to be upregulated in various cancer types and associated with metastasis and recurrence of hepatocellular carcinoma. Both gain- and loss-of-function studies revealed that STMP1 increased dynamin-related protein 1 (DRP1) activation to promote mitochondrial fission and enhanced migration of tumor cells. STMP1 silencing inhibited in vivo tumor metastasis in xenograft mouse models. Overexpression of STMP1 led to redistribution of mitochondria to the leading edge of cells and enhanced lamellipodia formation. Treatment with a DRP1 inhibitor abrogated the promotive effect of STMP1 on mitochondrial fission, lamellipodia formation, and tumor cell migration in vitro and metastasis in vivo. Furthermore, STMP1 interacted with myosin heavy chain 9 (MYH9), the subunit of non-muscle myosin II, and silencing MYH9 abrogated STMP1-induced DRP1 activation, mitochondrial fission, and cell migration. Collectively, this study identifies STMP1 as a critical regulator of metastasis and a novel unit of the mitochondrial fission protein machinery, providing a potential therapeutic target for treating metastases.

DOI: https://doi.org/10.1158/0008-5472.CAN-21-3910