Transcription elongation rate has a tissue-specific impact on alternative cleavage and polyadenylation in Drosophila melanogaster.
Transcription elongation rate has a tissue-specific impact on alternative cleavage and polyadenylation in Drosophila melanogaster.
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DOI：
10.1261/rna.062661.117
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发表时间：
2017-12
期刊：
影响因子：
--
通讯作者：
Moreira A
中科院分区：
文献类型：
--
作者：
Liu X;Freitas J;Zheng D;Oliveira MS;Hoque M;Martins T;Henriques T;Tian B;Moreira A
选择性多聚腺苷酸化（阿帕）是一种从单个基因产生具有不同3′ UTR和/或编码序列的多种mRNA异构体的机制。在这里，使用3′区域提取和深度测序（3′READS），我们系统地绘制了黑腹果蝇中的切割和多聚腺苷酸化位点（PAS），扩展了以前在该物种中发现的PAS的总库，特别是那些位于富含A的基因组序列中的PAS。顺式元件分析显示不同的序列基序周围飞PAS相比，哺乳动物的，包括更丰富的上游UAUA元件和下游UGUG元件不太突出的存在。我们发现，超过75%的果蝇mRNA基因进行阿帕。与身体相比，头部组织倾向于使用远端PAS，导致具有长3′ UTR以及远端末端外显子的阿帕亚型优先表达。阿帕位点之间的距离和PAS的内含子位置是身体和头部之间阿帕差异的重要参数，表明不同的PAS选择背景。对RpII 215 C4突变株（其携带具有较慢延伸速率的突变RNA聚合酶II（RNAPII））的阿帕分析显示，转录延伸速率降低50%会导致在3′ UTR和内含子中更多使用近端较弱PAS的温和趋势，与阿帕调节的“先到先得”模型一致。然而，在头部没有观察到这种趋势，这表明神经元细胞中存在不同的调控背景。总之，我们的数据扩大了PAS收集果蝇和揭示阿帕调节RNAPII伸长速率的组织特异性效果。
Alternative 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 when 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 when 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 reveal a tissue-specific effect of APA regulation by RNAPII elongation rate.
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