Transcription elongation rate has a tissue-specific impact on alternative cleavage and polyadenylation in Drosophila melanogaster.
- Xiaochuan Liu1,
- Jaime Freitas2,
- Dinghai Zheng1,
- Mainul Hoque1,
- Marta S. Oliveira2,
- Torcato Martins2,
- Telmo Henriques2,
- Bin Tian1,3 and
- Alexandra Moreira2
- ↵* Corresponding author; email: btian{at}rutgers.edu
Abstract
Alternative cleavage and polyadenylation (APA) is a mechanism that generates multiple mRNA isoforms with different 3’UTRs and/or coding sequences from a single gene. Here using 3’ Region Extraction And Deep Sequencing (3’READS), we have systematically mapped cleavage and polyadenylation sites (PASs) in Drosophila melanogaster, expanding the total repertoire of PASs previously identified for the species, especially those located in A-rich genomic sequences. cis-element analysis revealed distinct sequence motifs around fly PASs as compared to mammalian ones, including the greater enrichment of upstream UAUA elements and the less prominent presence of downstream UGUG elements. We found that over 75% of mRNA genes in Drosophila melanogaster undergo APA. The head tissue tends to use distal PASs as compared to the body, leading to preferential expression of APA isoforms with long 3’UTRs as well as with distal terminal exons. The distance between the APA sites and intron location of PAS are important parameters for APA difference between body and head, suggesting distinct PAS selection contexts. APA analysis of the RpII215C4 mutant strain, which harbors a mutant RNA polymerase II (RNAPII) with a slower elongation rate, revealed that a 50% decrease in transcriptional elongation rate leads to a mild trend of more usage of proximal, weaker PASs, both in 3’UTRs and in introns, consistent with the ‘first come, first served’ model of APA regulation. However, this trend was not observed in the head, suggesting a different regulatory context in neuronal cells. Together, our data expand the PAS collection for Drosophila melanogaster and reveals a tissue-specific effect of APA regulation by RNAPII elongation rate.
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- Received June 22, 2017.
- Accepted August 18, 2017.
- Published by Cold Spring Harbor Laboratory Press for the RNA Society
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