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Overlapping Activities of ELAV/Hu Family RNA Binding Proteins Specify the Extended Neuronal 3' UTR Landscape in Drosophila.

ABSTRACT: 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.

SUBMITTER: Wei L

PROVIDER: S-EPMC7546445 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Overlapping activities of ELAV/Hu family RNA binding proteins specify the extended neuronal 3' UTR landscape in Drosophila

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Overlapping activities of ELAV/Hu family RNA binding proteins specify the extended neuronal 3' UTR landscape in Drosophila [S2 3-seq]

Project description:The goals of this study are to establish a cell line based analysis platform to unbiasedly evaluate the capabilities of Elav/Hu family RNA binding proteins in regulating neural specific 3' UTR extension; and perform quantitative analysis of global 3' UTR extension regulated by individual Elav/Hu family RNA binding protein. We reported that in non-neural tissue context such as S2R+ cells, with the overexpression of wildtype Elav, Rbp9 and Fne, we observed global 3' UTR extensions for hundreds of genes, whose 3' UTR extension corespond with those detected in head; also, RNA rocognition motif mutant versions of Elav, Rbp9 and Fne loss the ability to regulate the generation of neural specific 3' UTR extension. We reported here for the first time, we show quantitative comparison between Elav/Hu family RNA binding proteins in regulating neural specific 3' UTR landscape and imply the overlapping activities of Elav/Hu family RNA binding proteins specifying neural 3' UTR landscape in Drosophila.

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Overlapping activities of ELAV/Hu family RNA binding proteins specify the extended neuronal 3' UTR landscape in Drosophila [L1 CNS 3'seq]

Project description:The goal of this study is to perform quantitative comparison of transcriptome-wide 3'-end features of Drosophila melanogaster 1st instar larvae central neural system (L1CNS) from three genotypes: Canton-S, elav5 single mutant, and elav5/fne double mutant; Total RNAs were extracted from dissected L1CNS of Drosophila melanogaster Canton-S, elav5 single mutant, and elav5/fne double mutant; 3'-end sequencing libraries were prepared using Lexogen QuantSeq 3′ mRNA-Seq Library Prep Kit REV for Illumina with replicates for each genotype; final cDNA libraries were sequenced on Illumina HiSeq-1000 sequencer with SE-50 mode. 3'-end sequencing data were mapped onto the corresponding UCSC genome assemblies: Drosophila melanogaster (dm6) and 3′ end clusters were derived and quantified within a 25 bp window. We found that L1CNS from Canton-S expresses neural specific 3' UTR extensions like head, while in L1CNS from elav5 single mutant, global neural specific 3' UTR extensions are not significantly lost, but in elav5/fne double mutant L1CNS, there is a dramatic loss of neural specific 3' UTR extensions. We reported for the first time demonstration of trans-acting factors that globally maintain this very distinctive tissue-specific APA landscape.

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Overlapping activities of ELAV/Hu family RNA binding proteins specify the extended neuronal 3' UTR landscape in Drosophila

Project description:Overlapping activities of ELAV/Hu family RNA binding proteins specify the extended neuronal 3' UTR landscape in Drosophila

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Overlapping activities of ELAV/Hu family RNA binding proteins specify the extended neuronal 3' UTR landscape in Drosophila [S2 3-seq]

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