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裂殖酵母减数分裂可变剪接异构体的动态格局。

The dynamic landscape of fission yeast meiosis alternative-splice isoforms.

作者信息

Kuang Zheng, Boeke Jef D, Canzar Stefan

机构信息

Institute for Systems Genetics, NYU Langone Medical Center, New York, New York 10016, USA.

Department of Biochemistry and Molecular Pharmacology, NYU Langone Medical Center, New York, New York 10016, USA.

出版信息

Genome Res. 2017 Jan;27(1):145-156. doi: 10.1101/gr.208041.116. Epub 2016 Nov 17.

Abstract

Alternative splicing increases the diversity of transcriptomes and proteomes in metazoans. The extent to which alternative splicing is active and functional in unicellular organisms is less understood. Here, we exploit a single-molecule long-read sequencing technique and develop an open-source software program called SpliceHunter to characterize the transcriptome in the meiosis of fission yeast. We reveal 14,353 alternative splicing events in 17,669 novel isoforms at different stages of meiosis, including antisense and read-through transcripts. Intron retention is the major type of alternative splicing, followed by alternate "intron in exon." Seven hundred seventy novel transcription units are detected; 53 of the predicted proteins show homology in other species and form theoretical stable structures. We report the complexity of alternative splicing along isoforms, including 683 intra-molecularly co-associated intron pairs. We compare the dynamics of novel isoforms based on the number of supporting full-length reads with those of annotated isoforms and explore the translational capacity and quality of novel isoforms. The evaluation of these factors indicates that the majority of novel isoforms are unlikely to be both condition-specific and translatable but consistent with the possibility of biologically functional novel isoforms. Moreover, the co-option of these unusual transcripts into newly born genes seems likely. Together, the results of this study highlight the diversity and dynamics at the isoform level in the sexual development of fission yeast.

摘要

可变剪接增加了后生动物转录组和蛋白质组的多样性。单细胞生物中可变剪接的活跃程度和功能尚不太清楚。在此,我们利用单分子长读长测序技术,开发了一个名为SpliceHunter的开源软件程序,以表征裂殖酵母减数分裂过程中的转录组。我们在减数分裂的不同阶段揭示了17,669个新异构体中的14,353个可变剪接事件,包括反义转录本和通读转录本。内含子保留是可变剪接的主要类型,其次是“外显子内的可变内含子”。检测到770个新的转录单元;预测的蛋白质中有53个在其他物种中显示出同源性并形成理论稳定结构。我们报告了沿异构体的可变剪接的复杂性,包括683个分子内共关联的内含子对。我们根据支持全长读段的数量将新异构体的动态与注释异构体的动态进行比较,并探索新异构体的翻译能力和质量。对这些因素的评估表明,大多数新异构体不太可能既是条件特异性的又是可翻译的,但与具有生物学功能的新异构体的可能性一致。此外,这些不寻常的转录本被新生成的基因共同选择似乎是可能的。总之,这项研究的结果突出了裂殖酵母有性发育过程中异构体水平的多样性和动态性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a5/5204338/3d0faa8020bc/145f01.jpg

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