Full Text:   <970>

Summary:  <946>

CLC number: Q752

On-line Access: 2019-10-09

Received: 2019-06-24

Revision Accepted: 2019-07-30

Crosschecked: 2019-09-12

Cited: 0

Clicked: 1757

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2019 Vol.20 No.11 P.920-927


Alternative role of noncoding RNAs: coding and noncoding properties

Author(s):  Gui-Zhen Zheng, Wei Li, Zhi-Yong Liu

Affiliation(s):  Department of Emergency Internal Medicine, Shanghai East Hospital, Tongji University, Shanghai 200120, China; more

Corresponding email(s):   liuzy271@163.com

Key Words:  Non-coding RNA, Biological function, Micropeptides, Cellular stress

Gui-Zhen Zheng, Wei Li, Zhi-Yong Liu. Alternative role of noncoding RNAs: coding and noncoding properties[J]. Journal of Zhejiang University Science B, 2019, 20(11): 920-927.

@article{title="Alternative role of noncoding RNAs: coding and noncoding properties",
author="Gui-Zhen Zheng, Wei Li, Zhi-Yong Liu",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Alternative role of noncoding RNAs: coding and noncoding properties
%A Gui-Zhen Zheng
%A Wei Li
%A Zhi-Yong Liu
%J Journal of Zhejiang University SCIENCE B
%V 20
%N 11
%P 920-927
%@ 1673-1581
%D 2019
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1900336

T1 - Alternative role of noncoding RNAs: coding and noncoding properties
A1 - Gui-Zhen Zheng
A1 - Wei Li
A1 - Zhi-Yong Liu
J0 - Journal of Zhejiang University Science B
VL - 20
IS - 11
SP - 920
EP - 927
%@ 1673-1581
Y1 - 2019
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1900336

Noncoding RNAs (ncRNAs) have played a critical role in cellular biological functions. Recently, some peptides or proteins originating from annotated ncRNAs were identified in organism development and various diseases. Here, we briefly review several novel peptides translated by annotated ncRNAs and related key functions. In addition, we summarize the potential mechanism of bifunctional ncRNAs and propose a specific “switch” triggering the transformation from the noncoding to the coding state under certain stimuli or cellular stress. The coding properties of ncRNAs and their peptide products may provide a novel horizon in proteomic research and can be regarded as a potential therapeutic target for the treatment of various diseases.



Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Anderson DM, Anderson KM, Chang CL, et al., 2015. A micropeptide encoded by a putative long noncoding RNA regulates muscle performance. Cell, 160(4):595-606.

[2]Ash PEA, Bieniek KF, Gendron TF, et al., 2013. Unconventional translation of C9ORF72 GGGGCC expansion generates insoluble polypeptides specific to c9FTD/ALS. Neuron, 77(4):639-646.

[3]Aspden JL, Eyre-Walker YC, Phillips RJ, et al., 2014. Extensive translation of small open reading frames revealed by Poly-Ribo-Seq. Elife, 3:e03528.

[4]Basrai MA, Hieter P, Boeke JD, 1997. Small open reading frames: beautiful needles in the haystack. Genome Res, 7(8):768-771.

[5]Bi PP, Ramirez-Martinez A, Li H, et al., 2017. Control of muscle formation by the fusogenic micropeptide myomixer. Science, 356(6335):323-327.

[6]Calviello L, Mukherjee N, Wyler E, et al., 2016. Detecting actively translated open reading frames in ribosome profiling data. Nat Methods, 13(2):165-170.

[7]Carninci P, Kasukawa T, Katayama S, et al., 2005. The transcriptional landscape of the mammalian genome. Science, 309(5740):1559-1563.

[8]Cech TR, Steitz JA, 2014. The noncoding RNA revolution-trashing old rules to forge new ones. Cell, 157(1):77-94.

[9]Chang KJ, Wang CC, 2004. Translation initiation from a naturally occurring non-AUG codon in Saccharomyces cerevisiae. J Biol Chem, 279(14):13778-13785.

[10]Chew GL, Pauli A, Rinn JL, et al., 2013. Ribosome profiling reveals resemblance between long non-coding RNAs and 5' leaders of coding RNAs. Development, 140(13):2828-2834.

[11]Chu Q, Ma J, Saghatelian A, 2015. Identification and characterization of sORF-encoded polypeptides. Crit Rev Biochem Mol Biol, 50(2):134-141.

[12]Costa FF, 2005. Non-coding RNAs: new players in eukaryotic biology. Gene, 357(2):83-94.

[13]Crappé J, van Criekinge W, Trooskens G, et al., 2013. Combining in silico prediction and ribosome profiling in a genome-wide search for novel putatively coding sORFs. BMC Genomics, 14:648.

[14]den Boon JA, Diaz A, Ahlquist P, 2010. Cytoplasmic viral replication complexes. Cell Host Microbe, 8(1):77-85.

[15]Dey BK, Mueller AC, Dutta A, 2014. Long non-coding RNAs as emerging regulators of differentiation, development, and disease. Transcription, 5(4):e944014.

[16]Eddy SR, 1999. Noncoding RNA genes. Curr Opin Genet Dev, 9(6):695-699.

[17]Gore-Panter SR, Hsu J, Barnard J, et al., 2016. PANCR, the PITX2 adjacent noncoding RNA, is expressed in human left atria and regulates PITX2c expression. Circ Arrhythm Electrophysiol, 9(1):e003197.

[18]Grelet S, Link LA, Howley B, et al., 2017. A regulated PNUTS mRNA to lncRNA splice switch mediates EMT and tumour progression. Nat Cell Biol, 19(9):1105-1115.

[19]Hanada K, Higuchi-Takeuchi M, Okamoto M, et al., 2013. Small open reading frames associated with morphogenesis are hidden in plant genomes. Proc Natl Acad Sci USA, 110(6):2395-2400.

[20]Hemm MR, Paul BJ, Schneider TD, et al., 2008. Small membrane proteins found by comparative genomics and ribosome binding site models. Mol Microbiol, 70(6):1487-1501.

[21]Hon CC, Ramilowski JA, Harshbarger J, et al., 2017. An atlas of human long non-coding RNAs with accurate 5' ends. Nature, 543(7644):199-204.

[22]Huang JZ, Chen M, Chen D, et al., 2017. A peptide encoded by a putative lncRNA HOXB-AS3 suppresses colon cancer growth. Mol Cell, 68(1):171-184.e176.

[23]Kearse MG, Wilusz JE, 2017. Non-AUG translation: a new start for protein synthesis in eukaryotes. Genes Dev, 31(17):1717-1731.

[24]Komar AA, Hatzoglou M, 2011. Cellular IRES-mediated translation: the war of ITAFs in pathophysiological states. Cell Cycle, 10(2):229-240.

[25]Kondo T, Hashimoto Y, Kato K, et al., 2007. Small peptide regulators of actin-based cell morphogenesis encoded by a polycistronic mRNA. Nat Cell Biol, 9(6):660-665.

[26]Kondo T, Plaza S, Zanet J, et al., 2010. Small peptides switch the transcriptional activity of shavenbaby during Drosophila embryogenesis. Science, 329(5989):336-339.

[27]Legnini I, di Timoteo G, Rossi F, et al., 2017. Circ-ZNF609 is a circular RNA that can be translated and functions in myogenesis. Mol Cell, 66(1):22-37.e9.

[28]Leprivier G, Rotblat B, Khan D, et al., 2015. Stress-mediated translational control in cancer cells. Biochim Biophys Acta, 1849(7):845-860.

[29]Li ZG, Hao S, Yin HQ, et al., 2016. Autophagy ameliorates cognitive impairment through activation of PVT1 and apoptosis in diabetes mice. Behav Brain Res, 305:265-277.

[30]Liberman N, Gandin V, Svitkin YV, et al., 2015. DAP5 associates with eIF2β and eIF4AI to promote internal ribosome entry site driven translation. Nucleic Acids Res, 43(7):3764-3775.

[31]Liu AF, Liu SR, 2016. Noncoding RNAs in growth and death of cancer cells. In: Song EW (Ed.), The Long and Short Non-coding RNAs in Cancer Biology. Springer, Singapore, p.137-172.

[32]Lozano G, Trapote A, Ramajo J, et al., 2015. Local RNA flexibility perturbation of the IRES element induced by a novel ligand inhibits viral RNA translation. RNA Biol, 12(5):555-568.

[33]Magny EG, Pueyo JI, Pearl FMG, et al., 2013. Conserved regulation of cardiac calcium uptake by peptides encoded in small open reading frames. Science, 341(6150):1116-1120.

[34]Matsumoto A, Pasut A, Matsumoto M, et al., 2017. mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide. Nature, 541(7636):228-232.

[35]Min KW, Davila S, Zealy RW, et al., 2017. eIF4E phosphorylation by MST1 reduces translation of a subset of mRNAs, but increases lncRNA translation. Biochim Biophys Acta, 1860(7):761-772.

[36]Mori K, Weng SM, Arzberger T, et al., 2013. The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD/ALS. Science, 339(6125):1335-1338.

[37]Mumtaz MAS, Couso JP, 2015. Ribosomal profiling adds new coding sequences to the proteome. Biochem Soc Trans, 43(6):1271-1276.

[38]Nam JW, Choi SW, You BH, 2016. Incredible RNA: dual functions of coding and noncoding. Mol Cells, 39(5): 367-374.


[40]Nelson BR, Makarewich CA, Anderson DM, et al., 2016. A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle. Science, 351(6270):271-275.

[41]Okamoto M, Higuchi-Takeuchi M, Shimizu M, et al., 2014. Substantial expression of novel small open reading frames in Oryza sativa. Plant Signal Behav, 9(2):e27848.

[42]Pamudurti NR, Bartok O, Jens M, et al., 2017. Translation of circRNAs. Mol Cell, 66(1):9-21.e7.

[43]Pauli A, Norris ML, Valen E, et al., 2014. Toddler: an embryonic signal that promotes cell movement via Apelin receptors. Science, 343(6172):1248636.

[44]Pueyo JI, Magny EG, Sampson CJ, et al., 2016. Hemotin, a regulator of phagocytosis encoded by a small ORF and conserved across metazoans. PLoS Biol, 14(3):e1002395.

[45]Röhrig H, Schmidt J, Miklashevichs E, et al., 2002. Soybean ENOD40 encodes two peptides that bind to sucrose synthase. Proc Natl Acad Sci USA, 99(4):1915-1920.

[46]Sampath K, Ephrussi A, 2016. CncRNAs: RNAs with both coding and non-coding roles in development. Development, 143(8):1234-1241.

[47]Slavoff SA, Mitchell AJ, Schwaid AG, et al., 2013. Peptidomic discovery of short open reading frame-encoded peptides in human cells. Nat Chem Biol, 9(1):59-64.

[48]Sonenberg N, Hinnebusch AG, 2009. Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell, 136(4):731-745.

[49]Stammers AN, Susser SE, Hamm NC, et al., 2015. The regulation of sarco(endo)plasmic reticulum calcium-ATPases (SERCA). Can J Physiol Pharmacol, 93(10):843-854.

[50]Takahashi K, Maruyama M, Tokuzawa Y, et al., 2005. Evolutionarily conserved non-AUG translation initiation in NAT1/p97/DAP5 (EIF4G2). Genomics, 85(3):360-371.

[51]Vandin F, Clay P, Upfal E, et al., 2012. Discovery of mutated subnetworks associated with clinical data in cancer. In: Altman RB, Dunker AK, Hunter L, et al. (Eds.), Pacific Symp on Biocomputing 2012. Kohala Coast, Hawaii, USA, p.55-66.

[52]Wang Y, Wang ZF, 2015. Efficient backsplicing produces translatable circular mRNAs. RNA, 21(2):172-179.

[53]Williamson L, Saponaro M, Boeing S, et al., 2017. UV irradiation induces a non-coding RNA that functionally opposes the protein encoded by the same gene. Cell, 168(5):843-855.e13.

[54]Xie N, Liu G, 2015. ncRNA-regulated immune response and its role in inflammatory lung diseases. Am J Physiol Lung Cell Mol Physiol, 309(10):L1076-L1087.

[55]Xu ZJ, Yan YL, Qian L, et al., 2017. Long non-coding RNAs act as regulators of cell autophagy in diseases. Oncol Rep, 37(3):1359-1366.

[56]Yang Y, Fan XJ, Mao MW, et al., 2017. Extensive translation of circular RNAs driven by N6-methyladenosine. Cell Res, 27(5):626-641.

[57]Zu T, Gibbens B, Doty NS, et al., 2011. Non-ATG-initiated translation directed by microsatellite expansions. Proc Natl Acad Sci USA, 108(1):260-265.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2022 Journal of Zhejiang University-SCIENCE