bims-micpro 2021-12-05 papers

Chembiochem. 2021 Dec 04.

The Small Open Reading Frame-encoded Peptides: Advances in Methodologies and Functional Studies.

Lei Chen, Ying Yang, Yuanliang Zhang, Kecheng Li, Hongmin Cai, Hongwei Wang, Qian Zhao.

Small open reading frames are an important class of genes with less than 100 codons. They were historically annotated as noncoding or even junk sequences. In recent years, accumulating evidence suggested that sORFs could encode a considerable number of polypeptides, many of which played important roles in both physiology and disease pathology. However, it has been technically challenging to directly detect the sORF-encoded peptides (SEPs). Here, we discuss the latest advance in methodologies for identifying SEPs with mass spectrometry, as well as the progress on functional studies of SEPs.

Keywords: Mass spectrometry; functions; proteomics; sORF-encoded peptides; small open reading frames

DOI: https://doi.org/10.1002/cbic.202100534

Trends Cell Biol. 2021 Nov 26. pii: S0962-8924(21)00226-9. [Epub ahead of print]

The dark proteome: translation from noncanonical open reading frames.

Bradley W Wright, Zixin Yi, Jonathan S Weissman, Jin Chen.

Omics-based technologies have revolutionized our understanding of the coding potential of the genome. In particular, these studies revealed widespread unannotated open reading frames (ORFs) throughout genomes and that these regions have the potential to encode novel functional (micro-)proteins and/or hold regulatory roles. However, despite their genomic prevalence, relatively few of these noncanonical ORFs have been functionally characterized, likely in part due to their under-recognition by the broader scientific community. The few that have been investigated in detail have demonstrated their essentiality in critical and divergent biological processes. As such, here we aim to discuss recent advances in understanding the diversity of noncanonical ORFs and their roles, as well as detail biologically important examples within the context of the mammalian genome.

Keywords: CRISPR; microproteins; noncanonical ORFs; ribosome profiling; short ORFs; translation

DOI: https://doi.org/10.1016/j.tcb.2021.10.010

J Cachexia Sarcopenia Muscle. 2021 Nov 30.

Microproteins in skeletal muscle: hidden keys in muscle physiology.

Bernardo Bonilauri, Bruno Dallagiovanna.

Recent advances in the transcriptomics, translatomics, and proteomics have led us to the exciting new world of functional endogenous microproteins. These microproteins have a small size and are derived from small open reading frames (smORFs) of RNAs previously annotated as non-coding (e.g. lncRNAs and circRNAs) as well as from untranslated regions and canonical mRNAs. The presence of these microproteins reveals a much larger translatable portion of the genome, shifting previously defined dogmas and paradigms. These findings affect our view of organisms as a whole, including skeletal muscle tissue. Emerging evidence demonstrates that several smORF-derived microproteins play crucial roles during muscle development (myogenesis), maintenance, and regeneration, as well as lipid and glucose metabolism and skeletal muscle bioenergetics. These microproteins are also involved in processes including physical activity capacity, cellular stress, and muscular-related diseases (i.e. myopathy, cachexia, atrophy, and muscle wasting). Given the role of these small proteins as important key regulators of several skeletal muscle processes, there are rich prospects for the discovery of new microproteins and possible therapies using synthetic microproteins.

Keywords: Microproteins; Muscle; lncRNAs; ncRNAs; smORF

DOI: https://doi.org/10.1002/jcsm.12866