Micropeptides Encoded in Transcripts Previously Identified as Long Noncoding RNAs: A New Chapter in Transcriptomics and Proteomics

Yeasmin, Fouzia; Yada, Tetsushi; Akimitsu, Nobuyoshi

doi:10.3389/fgene.2018.00144

Cited by 91 publications

(77 citation statements)

References 77 publications

(108 reference statements)

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“…For example, Xist has evolved into the ncRNA through the process of pseudogenization, during which proto-Xist had lost its protein-coding function and its flanking genes had turned into pseudogenes (Duret et al, 2006). On the contrary, micropeptide-encoding regions may be incorrectly classified as non-coding due to their size (Yeasmin et al, 2018). Next, the absence of ORF conservation does not guarantee an absence of protein-coding potential.…”

Section: Introductionmentioning

confidence: 99%

ncRNAs: New Players in Mitochondrial Health and Disease?

Gusic

2020

Front. Genet.

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The regulation of mitochondrial proteome is unique in that its components have origins in both mitochondria and nucleus. With the development of OMICS technologies, emerging evidence indicates an interaction between mitochondria and nucleus based not only on the proteins but also on the non-coding RNAs (ncRNAs). It is now accepted that large parts of the non-coding genome are transcribed into various ncRNA species. Although their characterization has been a hot topic in recent years, the function of the majority remains unknown. Recently, ncRNA species microRNA (miRNA) and long-non coding RNAs (lncRNA) have been gaining attention as direct or indirect modulators of the mitochondrial proteome homeostasis. These ncRNA can impact mitochondria indirectly by affecting transcripts encoding for mitochondrial proteins in the cytoplasm. Furthermore, reports of mitochondria-localized miRNAs, termed mitomiRs, and lncRNAs directly regulating mitochondrial gene expression suggest the import of RNA to mitochondria, but also transcription from the mitochondrial genome. Interestingly, ncRNAs have been also shown to hide small open reading frames (sORFs) encoding for small functional peptides termed micropeptides, with several examples reported with a role in mitochondria. In this review, we provide a literature overview on ncRNAs and micropeptides found to be associated with mitochondrial biology in the context of both health and disease. Although reported, small study overlap and rare replications by other groups make the presence, transport, and role of ncRNA in mitochondria an attractive, but still challenging subject. Finally, we touch the topic of their potential as prognosis markers and therapeutic targets.

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Section: Introductionmentioning

confidence: 99%

ncRNAs: New Players in Mitochondrial Health and Disease?

Gusic

2020

Front. Genet.

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“…These nORFs are pervasive throughout the genome and are observed in both the coding and non coding regions 1,7 . They are variously classified as small ORFs (sORFs) 8,9 which are 1-100 amino acids in length, altORFs 10 , which are proteins in alternate frames to known proteins, Denovogenes 11 or Orphan genes 12 , Pseudogenes 1,13 , and many ncRNAs have been shown to have coding potential [14][15][16][17][18] . These new discoveries challenge traditionally held conservative definitions of ORF, as used until the recent past 19 .…”

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confidence: 99%

Proteins encoded by Novel ORFs have increased disorder but can be biochemically regulated and harbour pathogenic mutations

Jagannathan

Meena

Bhayankaram

et al. 2019

Preprint

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Recent advances in proteogenomics indicate that protein or protein-like products can be encoded by previously uncharacterized Open Reading Frames (ORFs) that we define as Novel Open Reading Frames (nORFs) 1 , 2 . Although it is yet unclear if these protein or protein-like products could possess any significant biological function hopes have been raised to target them for anticancer and antimicrobial therapy 3,4 . In this study, we used computational tools to systematically investigate these novel protein sequences for their propensities toward structural disorder, post-translational modifications (PTM) and mutational densities. We found that these novel proteins have significantly higher disorder and similar PTM frequencies compared to known proteins. Although these regions were found to harbour deleterious mutations, we did not observe any correlation between the pathogenicity of mutations and their location (ordered/disordered) within these novel proteins. This study suggests that these nORFs encode an important class of proteins, that could undergo sequence, structural or regulatory changes during complex diseases, and hence warrant further study. Significance:Certain noncoding regions of the genome are known to make protein-like products. These protein-like products have significantly expanded the number of the cellular proteome but we dont know whether they are capable of performing biological functions. Here in this study, we have investigated all such putative protein-like products and analyzed whether they can form structures, whether hey harbour mutations, and whether they can be regulated by biochemical regulatory processes. Results from this study indicate that indeed these protein-like proteins can perform and be involved in all the above processes.

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“…This is because an unknown protein can be generated from an additional cistron of a mRNA encoding the canonical protein, since it has been estimated that the number of polycistronic mRNAs engendered from the human genome is colossal [38]. Many non-coding RNAs contain one or more cistrons as well [39][40][41], with GAPDH's non-coding RNA NR_152150.2 shown herein as a paradigm. It is also worth mentioning that NCBI database updates its data almost on a daily basis, often by adding more new RNA variants or protein isoforms to many genes' datasets.…”

Section: Discussionmentioning

confidence: 99%

ACTB and GAPDH proteins appear at multiple positions of SDS-PAGE and may not be suitable for serving as reference genes for the protein level determination in such techniques as Western blotting

Zhang

et al. 2020

Preprint

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Most human genes can produce multiple protein isoforms that should appear at multiple positions of polyacrylamide gel electrophoresis (PAGE) with sodium dodecyl sulfate (SDS), but most published results of Western blotting show only one protein. We performed SDS-PAGE of proteins from several human cell lines, isolated the proteins at the 72-, 55-, 48-, 40-, and 26-kD positions, and used liquid chromatography and tandem mass spectrometry (LC-MS/MS) to determine the protein identities. Although ACTB and GAPDH are 41.7-kD and 36-kD proteins, respectively, LC-MS/MS identified peptides of ACTB and GAPDH at all of these SDS-PAGE positions, making us wonder whether they produce some unknown protein isoforms. The NCBI (National Center for Biotechnology Information, USA) database lists only one ACTB mRNA but five GAPDH mRNAs and one non-coding RNA. The five GAPDH mRNAs encode three protein isoforms, while our bioinformatic analysis identified a 17.6-kD isoform encoded by the noncoding RNA. All LC-MS/MS-identified GAPDH peptides at all positions studied are unique, but some of the identified ACTB peptides are shared by ACTC1, ACTBL2, POTEF, POTEE, POTEI, and POTEJ. ACTC1 and ACTBL2 belong to the ACT family with great similarities to ACTB in protein sequence, whereas the four POTEs are ACTB-containing chimeric genes with the Cterminus of their proteins highly similar to ACTB. These data collectively disqualify GAPDH and ACTB from serving as the reference genes for determination of the protein level in such techniques as Western blotting, a leading role these two genes have been playing for decades in the biomedical research.

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Micropeptides Encoded in Transcripts Previously Identified as Long Noncoding RNAs: A New Chapter in Transcriptomics and Proteomics

Cited by 91 publications

References 77 publications

ncRNAs: New Players in Mitochondrial Health and Disease?

ncRNAs: New Players in Mitochondrial Health and Disease?

Proteins encoded by Novel ORFs have increased disorder but can be biochemically regulated and harbour pathogenic mutations

ACTB and GAPDH proteins appear at multiple positions of SDS-PAGE and may not be suitable for serving as reference genes for the protein level determination in such techniques as Western blotting

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