TY  - JOUR
A1  - Attig, Jan
A1  - Ruiz de los Mozos, Igor
A1  - Haberman, Nejc
A1  - Wang, Zhen
A1  - Emmett, Warren
A1  - Zarnack, Katharina
A1  - König, Julian
A1  - Ule, Jernej
T1  - Splicing repression allows the gradual emergence of new Alu-exons in primate evolution
T2  - eLife
N2  - Alu elements are retrotransposons that frequently form new exons during primate evolution. Here, we assess the interplay of splicing repression by hnRNPC and nonsense-mediated mRNA decay (NMD) in the quality control and evolution of new Alu-exons. We identify 3100 new Alu-exons and show that NMD more efficiently recognises transcripts with Alu-exons compared to other exons with premature termination codons. However, some Alu-exons escape NMD, especially when an adjacent intron is retained, highlighting the importance of concerted repression by splicing and NMD. We show that evolutionary progression of 3' splice sites is coupled with longer repressive uridine tracts. Once the 3' splice site at ancient Alu-exons reaches a stable phase, splicing repression by hnRNPC decreases, but the exons generally remain sensitive to NMD. We conclude that repressive motifs are strongest next to cryptic exons and that gradual weakening of these motifs contributes to the evolutionary emergence of new alternative exons.
KW  - Alu elements
KW  - evolutionary biology
KW  - exon evolution
KW  - genomics
KW  - human
KW  - nonsense mediated mRNA decay
KW  - pre-mRNA processing
KW  - splicing fidelity
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/44717
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-447175
SN  - 2050-084X
N1  - Copyright Attig et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
VL  - 5
IS  - e19545
SP  - 1
EP  - 27
PB  - eLife Sciences Publications
CY  - Cambridge
ER  -