GC-AG Introns Features in Long Non-coding and Protein-Coding Genes Suggest Their Role in Gene Expression Regulation.

GC-AG introns alternative splicing first intron long non-coding RNAs splice junctions

Journal

Frontiers in genetics
ISSN: 1664-8021
Titre abrégé: Front Genet
Pays: Switzerland
ID NLM: 101560621

Informations de publication

Date de publication:
2020
Historique:
received: 13 12 2019
accepted: 20 04 2020
entrez: 6 6 2020
pubmed: 6 6 2020
medline: 6 6 2020
Statut: epublish

Résumé

Long non-coding RNAs (lncRNAs) are recognized as an important class of regulatory molecules involved in a variety of biological functions. However, the regulatory mechanisms of long non-coding genes expression are still poorly understood. The characterization of the genomic features of lncRNAs is crucial to get insight into their function. In this study, we exploited recent annotations by GENCODE to characterize the genomic and splicing features of long non-coding genes in comparison with protein-coding ones, both in human and mouse. Our analysis highlighted differences between the two classes of genes in terms of their gene architecture. Significant differences in the splice sites usage were observed between long non-coding and protein-coding genes (PCG). While the frequency of non-canonical GC-AG splice junctions represents about 0.8% of total splice sites in PCGs, we identified a significant enrichment of the GC-AG splice sites in long non-coding genes, both in human (3.0%) and mouse (1.9%). In addition, we found a positional bias of GC-AG splice sites being enriched in the first intron in both classes of genes. Moreover, a significant shorter length and weaker donor and acceptor sites were found comparing GC-AG introns to GT-AG introns. Genes containing at least one GC-AG intron were found conserved in many species, more prone to alternative splicing and a functional analysis pointed toward their enrichment in specific biological processes such as DNA repair. Our study shows for the first time that GC-AG introns are mainly associated with lncRNAs and are preferentially located in the first intron. Additionally, we discovered their regulatory potential indicating the existence of a new mechanism of non-coding and PCGs expression regulation.

Identifiants

pubmed: 32499820
doi: 10.3389/fgene.2020.00488
pmc: PMC7242645
doi:

Types de publication

Journal Article

Langues

eng

Pagination

488

Informations de copyright

Copyright © 2020 Abou Alezz, Celli, Belotti, Lisa and Bione.

Références

Noncoding RNA. 2018 Aug 10;4(3):
pubmed: 30103474
Sci Adv. 2017 Sep 27;3(9):eaao2110
pubmed: 28959731
Sci Rep. 2017 Jan 05;7:40127
pubmed: 28054653
Nat Methods. 2017 Apr;14(4):417-419
pubmed: 28263959
In Silico Biol. 2006;6(3):237-42
pubmed: 16922687
Leukemia. 2018 Oct;32(10):2250-2262
pubmed: 29632340
Biol Direct. 2008 Jul 09;3:30
pubmed: 18613975
Mol Cell. 2004 Apr 23;14(2):221-31
pubmed: 15099521
Trends Genet. 2017 Oct;33(10):665-676
pubmed: 28870653
BMC Mol Biol. 2010 Apr 30;11:32
pubmed: 20433698
Exp Cell Res. 2008 Oct 15;314(17):3130-41
pubmed: 18775696
Genes Dev. 2011 Sep 15;25(18):1915-27
pubmed: 21890647
Nat Rev Genet. 2014 Jan;15(1):7-21
pubmed: 24296535
Nucleic Acids Res. 2019 Jan 25;47(2):911-928
pubmed: 30445574
Nucleic Acids Res. 2019 Jan 8;47(D1):D128-D134
pubmed: 30329098
Genome Res. 2017 Jun;27(6):1050-1062
pubmed: 28396519
J Comput Biol. 2004;11(2-3):377-94
pubmed: 15285897
Nat Protoc. 2009;4(1):44-57
pubmed: 19131956
Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):2876-81
pubmed: 23382218
Cell Cycle. 2013 Jul 1;12(13):2061-72
pubmed: 23759593
Trends Cell Biol. 2009 Sep;19(9):465-74
pubmed: 19716303
Genome Res. 2007 May;17(5):556-65
pubmed: 17387145
Nat Commun. 2016 Aug 17;7:12339
pubmed: 27531712
Wiley Interdiscip Rev RNA. 2018 May 31;:e1485
pubmed: 29851258
Nucleic Acids Res. 2014;42(16):10564-78
pubmed: 25123659
Genome Res. 2000 Jul;10(7):1001-10
pubmed: 10899149
Trends Biochem Sci. 2016 Jan;41(1):33-45
pubmed: 26682498
BMC Evol Biol. 2007 Oct 04;7:187
pubmed: 17916234
Nat Genet. 2000 May;25(1):25-9
pubmed: 10802651
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D493-6
pubmed: 14681465
Nucleic Acids Res. 2006;34(14):3955-67
pubmed: 16914448
Genome Res. 2012 Sep;22(9):1775-89
pubmed: 22955988
RNA. 2015 May;21(5):801-12
pubmed: 25802408
Front Genet. 2019 Feb 07;9:672
pubmed: 30792737
Nucleic Acids Res. 2002 Aug 1;30(15):3360-7
pubmed: 12140320
Nucleic Acids Res. 2001 Jun 15;29(12):2581-93
pubmed: 11410667
Nucleic Acids Res. 1994 May 11;22(9):1515-26
pubmed: 8202349
Cell Rep. 2012 Jul 26;2(1):62-8
pubmed: 22840397
Wiley Interdiscip Rev RNA. 2017 Jan;8(1):
pubmed: 27436689
Mol Biol Evol. 2014 Dec;31(12):3164-83
pubmed: 25158797
Genome Res. 2006 Jan;16(1):11-9
pubmed: 16344565
Trends Genet. 2017 Jul;33(7):464-478
pubmed: 28535931
Nature. 2016 Nov 17;539(7629):433-436
pubmed: 27783597
Front Genet. 2014 Jun 06;5:164
pubmed: 24936207
Nucleic Acids Res. 2018 Jan 4;46(D1):D308-D314
pubmed: 29140524
J Cell Biochem. 2018 Nov 11;:
pubmed: 30417553
Genome Res. 2012 Sep;22(9):1616-25
pubmed: 22955974
Genome Res. 2017 Jan;27(1):27-37
pubmed: 27927715
Genome Biol. 2018 Mar 23;19(1):40
pubmed: 29571299
Nature. 2016 Nov 17;539(7629):452-455
pubmed: 27783602
Life (Basel). 2016 Jul 15;6(3):
pubmed: 27429005
Genome Res. 2002 Jun;12(6):996-1006
pubmed: 12045153
Philos Trans R Soc Lond B Biol Sci. 2017 Feb 5;372(1713):
pubmed: 27994117
Cell Rep. 2015 May 19;11(7):1110-22
pubmed: 25959816
BMC Genomics. 2014 Jun 26;15:526
pubmed: 24964727
Nat Med. 2016 Aug;22(8):861-8
pubmed: 27376578
Nat Genet. 2017 Dec;49(12):1731-1740
pubmed: 29106417
Nucleic Acids Res. 2011 Sep 1;39(16):7077-91
pubmed: 21609956
Genome Res. 2005 Jan;15(1):111-9
pubmed: 15590946
Nature. 2013 Jul 18;499(7458):360-3
pubmed: 23792564
BMC Genomics. 2014 Jan 17;15:35
pubmed: 24438357
Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):882-6
pubmed: 17210920
Bioinformatics. 2018 Mar 15;34(6):920-927
pubmed: 29092009
Biomed Pharmacother. 2019 Mar;111:1447-1457
pubmed: 30841460
Nucleic Acids Res. 2013 Jan;41(Database issue):D246-51
pubmed: 23042674
Nucleic Acids Res. 2019 Jan 8;47(D1):D766-D773
pubmed: 30357393
Cell Stem Cell. 2016 May 5;18(5):637-52
pubmed: 26996597
Nucleic Acids Res. 2015 Jul 1;43(W1):W589-98
pubmed: 25897122
IUBMB Life. 2017 Nov;69(11):867-876
pubmed: 28960757
Cell. 2012 Jul 6;150(1):53-64
pubmed: 22770214
Inflamm Res. 2018 Dec;67(11-12):927-936
pubmed: 30310931
Nat Genet. 2015 Mar;47(3):199-208
pubmed: 25599403
Nucleic Acids Res. 2019 Jan 8;47(D1):D419-D426
pubmed: 30407594
Nature. 2001 Dec 20-27;414(6866):929-33
pubmed: 11780068
Biochim Biophys Acta Gene Regul Mech. 2019 Jun;1862(6):634-642
pubmed: 31042550
Nucleic Acids Res. 2019 Jan 8;47(D1):D330-D338
pubmed: 30395331
Nature. 2017 Mar 9;543(7644):199-204
pubmed: 28241135
Science. 2012 Dec 14;338(6113):1469-72
pubmed: 23239737
Science. 2015 May 8;348(6235):648-60
pubmed: 25954001

Auteurs

Monah Abou Alezz (M)

Computational Biology Unit, Institute of Molecular Genetics Luigi Luca Cavalli-Sforza, National Research Council, Pavia, Italy.

Ludovica Celli (L)

Computational Biology Unit, Institute of Molecular Genetics Luigi Luca Cavalli-Sforza, National Research Council, Pavia, Italy.

Giulia Belotti (G)

Computational Biology Unit, Institute of Molecular Genetics Luigi Luca Cavalli-Sforza, National Research Council, Pavia, Italy.

Antonella Lisa (A)

Computational Biology Unit, Institute of Molecular Genetics Luigi Luca Cavalli-Sforza, National Research Council, Pavia, Italy.

Silvia Bione (S)

Computational Biology Unit, Institute of Molecular Genetics Luigi Luca Cavalli-Sforza, National Research Council, Pavia, Italy.

Classifications MeSH