title: It's a bit over, is that ok? The subtle surplus from tandem alternative splicing.
abstract: Tandem alternative splice sites (TASS) form a defined class of alternative splicing and give rise to mRNA insertion/deletion variants with only small size differences. Previous work has confirmed evolutionary conservation of TASS elements while many cases show only low tissue specificity of isoform ratios. We pinpoint stochasticity and noise as important methodological issues for the dissection of TASS isoform patterns. Resolving such uncertainties, a recent report showed regulation in a cell culture system, with shifts of alternative splicing isoform ratios dependent on cell density. This novel type of regulation affects not only multiple TASS isoforms, but also other alternative splicing classes, in a concerted manner. Here, we discuss how specific regulatory network architectures may be realized through the novel regulation type and highlight the role of differential isoform functions as a key step in order to better understand the functional role of TASS.
authors.affiliation: a Fritz Lipmann Institute - Leibniz Institute on Aging ; Jena , Germany.
authors.forename: Karol
authors.initials: K
authors.lastname: Szafranski
authors.forename: Marcel
authors.initials: M
authors.lastname: Kramer
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002478:Cells, Cultured; D005091:Exons; D006801:Humans; D007438:Introns; D008322:Mammals; D020033:Protein Isoforms / Q000235:genetics* / Q000378:metabolism; D022821:RNA Splice Sites; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D018401:Sample Size; D017381:Spliceosomes / Q000737:chemistry / Q000378:metabolism; D013269:Stochastic Processes
chemical_list: D020033:Protein Isoforms; D022821:RNA Splice Sites; D012333:RNA, Messenger
keywords: AS, alternative splicing; NAGNAG; PCAS, physiologically triggered, concerted shift in alternative splicing; TASS, tandem alternative splice sites; splice site choice; splicing factors; splicing regulation; tandem alternative splice sites
references.citation: Genes Dev. 2011 Feb 15;25(4):373-84
references.pmid: 21325135
references.citation: Cell. 2008 Oct 17;135(2):216-26
references.pmid: 18957198
references.citation: Dev Cell. 2014 Feb 10;28(3):225-38
references.pmid: 24525185
references.citation: Nature. 1999 Nov 11;402(6758):207-10
references.pmid: 10647016
references.citation: Nucleic Acids Res. 2007;35(16):5487-98
references.pmid: 17704130
references.citation: Genetics. 2011 Mar;187(3):761-70
references.pmid: 21220357
references.citation: BMC Genomics. 2008;9:159
references.pmid: 18402682
references.citation: Mol Cell Biol. 2004 Dec;24(24):10505-14
references.pmid: 15572659
references.citation: Cold Spring Harb Perspect Biol. 2011 Jul;3(7). pii: a003707. doi: 10.1101/cshperspect.a003707
references.pmid: 21441581
references.citation: RNA. 2006 Dec;12(12):2047-56
references.pmid: 17053087
references.citation: PLoS Genet. 2006 Apr;2(4):e45
references.pmid: 16683028
references.citation: Nucleic Acids Res. 2014 Aug;42(14):8895-904
references.pmid: 25030907
references.citation: Genome Res. 2005 Oct;15(10):1388-92
references.pmid: 16204192
references.citation: Genome Res. 2011 Jul;21(7):1160-7
references.pmid: 21543516
references.citation: Genome Biol. 2012;13(2):143
references.pmid: 22356731
references.citation: BMC Mol Biol. 2010;11:34
references.pmid: 20459675
references.citation: Nucleic Acids Res. 2006;34(1):23-31
references.pmid: 16394021
references.citation: RNA. 2008 Apr;14(4):616-29
references.pmid: 18268022
references.citation: Electrophoresis. 2009 Nov;30(21):3674-81
references.pmid: 19862747
references.citation: Front Genet. 2013 Sep 17;4:178
references.pmid: 24062766
references.citation: PLoS Biol. 2012 Jan;10(1):e1001229
references.pmid: 22235189
references.citation: J Hum Genet. 2005;50(8):382-94
references.pmid: 16091834
references.citation: BMC Bioinformatics. 2010;11:216
references.pmid: 20429909
references.citation: Science. 2000 Oct 20;290(5491):523-7
references.pmid: 11039935
references.citation: Gene. 2005 Jan 3;344:1-20
references.pmid: 15656968
references.citation: Genome Biol. 2007;8(8):R154
references.pmid: 17672918
references.citation: Nat Genet. 2004 Dec;36(12):1255-7
references.pmid: 15516930
references.citation: Cell. 2001 Aug 10;106(3):319-29
references.pmid: 11509181
references.citation: Annu Rev Biochem. 2003;72:291-336
references.pmid: 12626338
references.citation: Nature. 2008 Nov 27;456(7221):470-6
references.pmid: 18978772
references.citation: Genes Dev. 2010 Jun 1;24(11):1073-4
references.pmid: 20516191
references.citation: Hum Mol Genet. 1998 Apr;7(4):709-14
references.pmid: 9499425
references.citation: Genetics. 2007 Mar;175(3):1079-87
references.pmid: 17179090
references.citation: Mol Cell Biol. 1996 Dec;16(12):6677-86
references.pmid: 8943322
references.citation: EMBO J. 1997 Nov 17;16(22):6793-803
references.pmid: 9362493
references.citation: Nucleic Acids Res. 2009 Jun;37(11):3569-79
references.pmid: 19359358
references.citation: Nature. 2007 Apr 19;446(7138):926-9
references.pmid: 17361132
references.citation: Genomics. 2006 Dec;88(6):855-64
references.pmid: 16920330
references.citation: Trends Genet. 2008 May;24(5):246-55
references.pmid: 18394746
references.citation: Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9618-22
references.pmid: 1658787
references.citation: Int J Biochem Cell Biol. 2007;39(11):2031-48
references.pmid: 17507279
references.citation: Mol Cell Biol. 2005 Apr;25(8):3232-46
references.pmid: 15798208