TY - JOUR
T1 - Intergenic Alu exonisation facilitates the evolution of tissue-specific transcript ends
AU - Tajnik, Mojca
AU - Vigilante, Alessandra
AU - Braun, Simon
AU - Hänel, Heike
AU - Luscombe, Nicholas M.
AU - Ule, Jernej
AU - Zarnack, Kathi
AU - König, Julian
N1 - Funding Information:
LOEWE programme Ubiquitin Networks (Ub-Net) of the State of Hesse (Germany) [K.Z.]; EMBO Short-Term Fellowship [M.T]. Funding for open access charge: Institute of Molecular Biology (IMB).
Publisher Copyright:
© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2015/9/22
Y1 - 2015/9/22
N2 - The 3′ untranslated regions (3′ UTRs) of transcripts serve as important hubs for posttranscriptional gene expression regulation. Here, we find that the exonisation of intergenic Alu elements introduced new terminal exons and polyadenylation sites during human genome evolution. While Alu exonisation from introns has been described previously, we shed light on a novel mechanism to create alternative 3′ UTRs, thereby opening opportunities for differential posttranscriptional regulation. On the mechanistic level, we show that intergenic Alu exonisation can compete both with alternative splicing and polyadenylation in the upstream gene. Notably, the Alu-derived isoforms are often expressed in a tissue-specific manner, and the Alu-derived 3′ UTRs can alter mRNA stability. In summary, we demonstrate that intergenic elements can affect processing of preceding genes, and elucidate how intergenic Alu exonisation can contribute to tissue-specific posttranscriptional regulation by expanding the repertoire of 3′ UTRs.
AB - The 3′ untranslated regions (3′ UTRs) of transcripts serve as important hubs for posttranscriptional gene expression regulation. Here, we find that the exonisation of intergenic Alu elements introduced new terminal exons and polyadenylation sites during human genome evolution. While Alu exonisation from introns has been described previously, we shed light on a novel mechanism to create alternative 3′ UTRs, thereby opening opportunities for differential posttranscriptional regulation. On the mechanistic level, we show that intergenic Alu exonisation can compete both with alternative splicing and polyadenylation in the upstream gene. Notably, the Alu-derived isoforms are often expressed in a tissue-specific manner, and the Alu-derived 3′ UTRs can alter mRNA stability. In summary, we demonstrate that intergenic elements can affect processing of preceding genes, and elucidate how intergenic Alu exonisation can contribute to tissue-specific posttranscriptional regulation by expanding the repertoire of 3′ UTRs.
UR - http://www.scopus.com/inward/record.url?scp=84975074328&partnerID=8YFLogxK
U2 - 10.1093/nar/gkv956
DO - 10.1093/nar/gkv956
M3 - Article
C2 - 26400176
AN - SCOPUS:84975074328
SN - 0305-1048
VL - 43
SP - 10492
EP - 10505
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 21
ER -