Yan Jun, Marr Thomas G
Institute of Arctic Biology, University of Alaska, Fairbanks, Alaska 99775-7000, USA.
Genome Res. 2005 Mar;15(3):369-75. doi: 10.1101/gr.3109605.
Alternative initiation, splicing, and polyadenylation are key mechanisms used by many organisms to generate diversity among mature mRNA transcripts originating from the same transcription unit. While previous computational analyses of alternative polyadenylation have focused on polyadenylation activities within or downstream of the normal 3'-terminal exons, we present the results of the first genome-wide analysis of patterns of alternative polyadenylation in the human, mouse, and rat genomes occurring over the entire transcribed regions of mRNAs using 3'-ESTs with poly(A) tails aligned to genomic sequences. Four distinct classes of patterns of alternative polyadenylation result from this analysis: tandem poly(A) sites, composite exons, hidden exons, and truncated exons. We estimate that at least 49% (human), 31% (mouse), and 28% (rat) of polyadenylated transcription units have alternative polyadenylation. A portion of these alternative polyadenylation events result in new protein isoforms.
可变起始、剪接和聚腺苷酸化是许多生物体用于在源自同一转录单元的成熟mRNA转录本中产生多样性的关键机制。虽然之前对可变聚腺苷酸化的计算分析主要集中在正常3'末端外显子内部或下游的聚腺苷酸化活性上，但我们展示了首次使用带有与基因组序列比对的poly(A)尾的3'-EST，对人类、小鼠和大鼠基因组中mRNA整个转录区域发生的可变聚腺苷酸化模式进行全基因组分析的结果。该分析产生了四类不同的可变聚腺苷酸化模式：串联poly(A)位点、复合外显子、隐蔽外显子和截短外显子。我们估计，至少49%（人类）、31%（小鼠）和28%（大鼠）的聚腺苷酸化转录单元存在可变聚腺苷酸化。这些可变聚腺苷酸化事件中的一部分会导致新的蛋白质异构体产生。
