TY - JOUR
T1 - Overlapping activities of ELAV/Hu family RNA binding proteins specify the extended neuronal 3' UTR landscape in Drosophila
AU - Wei, Lu
AU - Lee, Seungjae
AU - Majumdar, Sonali
AU - Zhang, Binglong
AU - Sanfilippo, Piero
AU - Joseph, Brian
AU - Miura, Pedro
AU - Soller, Matthias
AU - Lai, Eric
PY - 2020/10/1
Y1 - 2020/10/1
N2 - The tissue-specific deployment of highly extended neural 3′ UTR isoforms, generated by alternative polyadenylation (APA), is a broad and conserved feature of metazoan genomes. However, the factors and mechanisms that control neural APA isoforms are not well understood. Here, we show that three ELAV/Hu RNA binding proteins (Elav, Rbp9, and Fne) have similar capacities to induce a lengthened 3′ UTR landscape in an ectopic setting. These factors promote accumulation of chromatin-associated, 3′ UTR-extended, nascent transcripts, through inhibition of proximal polyadenylation site (PAS) usage. Notably, Elav represses an unannotated splice isoform of fne, switching the normally cytoplasmic Fne toward the nucleus in elav mutants. We use genomic profiling to reveal strong and broad loss of neural APA in elav/fne double mutant CNS, the first genetic background to largely abrogate this distinct APA signature. Overall, we demonstrate how regulatory interplay and functionally overlapping activities of neural ELAV/Hu RBPs drives the neural APA landscape.
AB - The tissue-specific deployment of highly extended neural 3′ UTR isoforms, generated by alternative polyadenylation (APA), is a broad and conserved feature of metazoan genomes. However, the factors and mechanisms that control neural APA isoforms are not well understood. Here, we show that three ELAV/Hu RNA binding proteins (Elav, Rbp9, and Fne) have similar capacities to induce a lengthened 3′ UTR landscape in an ectopic setting. These factors promote accumulation of chromatin-associated, 3′ UTR-extended, nascent transcripts, through inhibition of proximal polyadenylation site (PAS) usage. Notably, Elav represses an unannotated splice isoform of fne, switching the normally cytoplasmic Fne toward the nucleus in elav mutants. We use genomic profiling to reveal strong and broad loss of neural APA in elav/fne double mutant CNS, the first genetic background to largely abrogate this distinct APA signature. Overall, we demonstrate how regulatory interplay and functionally overlapping activities of neural ELAV/Hu RBPs drives the neural APA landscape.
KW - 3′ UTR
KW - APA
KW - CNS
KW - Drosophila
KW - Elav
KW - Hu
KW - RBP
KW - RNA binding protein
KW - alternative polyadenylation
KW - neuron
UR - https://www.cell.com/molecular-cell/home
UR - http://www.scopus.com/inward/record.url?scp=85091658974&partnerID=8YFLogxK
U2 - 10.1016/j.molcel.2020.09.007
DO - 10.1016/j.molcel.2020.09.007
M3 - Article
C2 - 33007254
SN - 1097-2765
VL - 80
SP - 140-155.e6
JO - Molecular Cell
JF - Molecular Cell
IS - 1
ER -