Extensive transcriptional heterogeneity revealed by isoform profiling.
Extensive transcriptional heterogeneity revealed by isoform profiling.
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作者：
转录功能由排列在单个RNA分子上的序列元件决定。转录本的变异可以影响mRNA的稳定性、定位和翻译，或者导致截短的蛋白质具有不同的亚细胞定位和功能。鉴于存在重叠的、可变的转录组异构体，确定转录组的功能影响需要识别全长转录体，而不仅仅是转录的基因组区域。在这里，通过联合确定数百万RNA分子的两个转录末端(TIF-Seq)，我们揭示了先前隐藏在重叠RNA分子中的广泛的异构体多样性层。转录本边界的变化似乎是规则而不是例外，即使在单一的酵母细胞群体中也是如此。每个蛋白质编码基因有超过26种主要转录异构体在酵母中表达。数以百计的短编码RNA和蛋白质的截短版本由替代的转录异构体同时编码，增加了蛋白质的多样性。此外，约70%的基因表达不同的转录后调控元件，串联基因经常产生重叠甚至双顺反子转录本。这种广泛的转录本多样性是由相对简单的真核基因组和有限的剪接产生的，并且是在遗传同质的细胞群体中产生的。我们的发现对基因组紧凑、进化和单细胞之间的表型多样性具有重要意义。他们还建议，在评估基因组的功能谱系时，应考虑异构体多样性和RNA丰度。
Transcript function is determined by sequence elements arranged on an individual RNA molecule. Variation in transcripts can affect mRNA stability, localization, and translation, or give rise to truncated proteins with differing subcellular localizations and functions. Given the existence of overlapping, variable transcript isoforms, determining the functional impact of the transcriptome requires identification of full-length transcripts, rather than just the genomic regions that are transcribed. Here, by jointly determining both transcript ends for millions of RNA molecules (TIF-Seq), we reveal an extensive layer of isoform diversity previously hidden among overlapping RNA molecules. Variation in transcript boundaries appears to be the rule rather than the exception, even within a single population of yeast cells. Over 26 major transcript isoforms per protein-coding gene were expressed in yeast. Hundreds of short coding RNAs and truncated versions of proteins are concomitantly encoded by alternative transcript isoforms, increasing protein diversity. In addition, ~70% of genes express alternative isoforms that vary in posttranscriptional regulatory elements, and tandem genes frequently produce overlapping or even bicistronic transcripts. This extensive transcript diversity is generated by a relatively simple eukaryotic genome with limited splicing, and within a genetically homogeneous population of cells. Our findings have implications for genome compaction, evolution, and phenotypic diversity between single cells. They also suggest that isoform diversity as well as RNA abundance should be considered when assessing the functional repertoire of genomes.
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影响因子：
4.4
作者：
Miura, Fumihito;Kawaguchi, Noriko;Yoshida, Mikio;Uematsu, Chihiro;Kito, Keiji;Sakaki, Yoshiyuki;Ito, Takashi
通讯作者：
Ito, Takashi
DOI：
10.1126/science.1224350
发表时间：
2012-11-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Tan-Wong SM;Zaugg JB;Camblong J;Xu Z;Zhang DW;Mischo HE;Ansari AZ;Luscombe NM;Steinmetz LM;Proudfoot NJ
通讯作者：
Proudfoot NJ
影响因子：
64.5
作者：
Ozsolak F;Kapranov P;Foissac S;Kim SW;Fishilevich E;Monaghan AP;John B;Milos PM
通讯作者：
Milos PM
影响因子：
64.5
作者：
Yao P;Potdar AA;Arif A;Ray PS;Mukhopadhyay R;Willard B;Xu Y;Yan J;Saidel GM;Fox PL
通讯作者：
Fox PL
影响因子：
10.5
作者：
Ungewitter, Erica;Scrable, Heidi
通讯作者：
Scrable, Heidi