Protein-coding potential of non-canonical open reading frames in human transcriptome

Hitesh Kore; Keshava K Datta; Shivashankar H Nagaraj; Harsha Gowda

doi:10.1016/j.bbrc.2023.09.068

Protein-coding potential of non-canonical open reading frames in human transcriptome

Biochem Biophys Res Commun. 2023 Dec 3:684:149040. doi: 10.1016/j.bbrc.2023.09.068. Epub 2023 Oct 13.

Authors

Hitesh Kore¹, Keshava K Datta², Shivashankar H Nagaraj³, Harsha Gowda⁴

Affiliations

¹ Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland, 4059, Australia; Cancer Precision Medicine Group, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Queensland, 4006, Australia; Faculty of Health, Queensland University of Technology, Brisbane, Queensland, 4059, Australia. Electronic address: hiteshugaram.kore@hdr.qut.edu.au.
² Proteomics and Metabolomics Platform, La Trobe University, Melbourne, VIC, 3083, Australia.
³ Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland, 4059, Australia; Faculty of Health, Queensland University of Technology, Brisbane, Queensland, 4059, Australia.
⁴ Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland, 4059, Australia; Cancer Precision Medicine Group, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Queensland, 4006, Australia; Faculty of Health, Queensland University of Technology, Brisbane, Queensland, 4059, Australia; Faculty of Medicine, The University of Queensland, Queensland, 4072, Australia. Electronic address: h.gowda@qut.edu.au.

PMID: 37897910
DOI: 10.1016/j.bbrc.2023.09.068

Abstract

In recent years, proteogenomics and ribosome profiling studies have identified a large number of proteins encoded by noncoding regions in the human genome. They are encoded by small open reading frames (sORFs) in the untranslated regions (UTRs) of mRNAs and long non-coding RNAs (lncRNAs). These sORF encoded proteins (SEPs) are often <150AA and show poor evolutionary conservation. A subset of them have been functionally characterized and shown to play an important role in fundamental biological processes including cardiac and muscle function, DNA repair, embryonic development and various human diseases. How many novel protein-coding regions exist in the human genome and what fraction of them are functionally important remains a mystery. In this review, we discuss current progress in unraveling SEPs, approaches used for their identification, their limitations and reliability of these identifications. We also discuss functionally characterized SEPs and their involvement in various biological processes and diseases. Lastly, we provide insights into their distinctive features compared to canonical proteins and challenges associated with annotating these in protein reference databases.

Keywords: Non-coding RNAs; Novel proteins; Protein-coding potential; SEPs.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Humans
Open Reading Frames / genetics
RNA, Long Noncoding* / genetics
RNA, Messenger / genetics
Reproducibility of Results
Transcriptome* / genetics

Substances

RNA, Long Noncoding
RNA, Messenger