Batra Ranjan, Manchanda Mini, Swanson Maurice S
a Department of Cellular and Molecular Medicine ; Institute for Genomic Medicine; UCSD Stem Cell Program; University of California ; San Diego , CA USA.
RNA Biol. 2015;12(6):597-602. doi: 10.1080/15476286.2015.1040974.
Alternative pre-mRNA processing greatly increases the coding capacity of the human genome and regulatory factors involved in RNA processing play critical roles in tissue development and maintenance. Indeed, abnormal functions of RNA processing factors have been associated with a wide range of human diseases from cancer to neurodegenerative disorders. While many studies have emphasized the importance of alternative splicing (AS), recent high-throughput sequencing efforts have also allowed global surveys of alternative polyadenylation (APA). For the majority of pre-mRNAs, as well as some non-coding transcripts such as lncRNAs, APA selects different 3'-ends and thus modulates the availability of regulatory sites recognized by trans-acting regulatory effectors, including miRs and RNA binding proteins (RBPs). Here, we compare the available technologies for assessing global polyadenylation patterns, summarize the roles of auxiliary factors on APA, and discuss the impact of differential polyA site (pA) selection in the determination of cell fate, transformation and disease.
可变前体mRNA加工极大地增加了人类基因组的编码能力，参与RNA加工的调控因子在组织发育和维持中发挥着关键作用。事实上，RNA加工因子的异常功能与从癌症到神经退行性疾病等广泛的人类疾病有关。虽然许多研究强调了可变剪接（AS）的重要性，但最近的高通量测序研究也使得对可变多聚腺苷酸化（APA）进行全球范围的调查成为可能。对于大多数前体mRNA以及一些非编码转录本（如lncRNA），APA选择不同的3'末端，从而调节包括miR和RNA结合蛋白（RBP）在内的反式作用调节效应物所识别的调控位点的可用性。在这里，我们比较了评估全球多聚腺苷酸化模式的现有技术，总结了辅助因子在APA中的作用，并讨论了差异多聚腺苷酸化位点（pA）选择在细胞命运决定、转化和疾病中的影响。
