An alternative transcriptome shapes cell fate transitions in yeast (TIF-seq)

Alternative mRNA isoforms and long noncoding RNAs (lncRNA) make up a large fraction of the transcriptome and play key functions in cell-fate programming. These transcripts often initiate upstream of coding gene promoters from alternative transcription start sites (TSS) where they can regulate gene expression in cis through transcription-coupled chromatin alterations. How, when and where transcription of alternative cis-acting RNAs regulates local gene expression remains poorly understood. Here, we use a high-resolution quantitative approach to study alternative TSS and transcript end site (TES) usage during three different cell fate transitions in yeast: entry into gametogenesis, commitment to meiotic divisions and return to vegetative growth. We propose that an alternative transcriptome of mRNA isoforms and lncRNAs shapes local gene expression during cell fate transitions. Hence, changes in the types and proportions of different RNAs transcribed at a locus are important inputs for gene expression at distinct stages of development.可变mRNA亚型（alternative mRNA isoforms）与长链非编码RNA（long noncoding RNAs, lncRNA）占转录组（transcriptome）的绝大部分比例，在细胞命运编程（cell-fate programming）中发挥关键调控作用。此类转录本通常从可变转录起始位点（alternative transcription start sites, TSS）处的编码基因启动子上游起始，并可通过转录偶联的染色质改变（transcription-coupled chromatin alterations）以顺式方式调控基因表达。目前，关于可变顺式作用RNA（cis-acting RNAs）的转录如何、何时以及在何处调控局部基因表达，仍尚未得到充分阐明。本研究采用高分辨率定量方法（high-resolution quantitative approach），探究酵母（yeast）中三类不同细胞命运转变（cell fate transitions）过程中的可变转录起始位点（TSS）与转录终止位点（transcript end site, TES）使用模式，这三类转变分别为配子发生（gametogenesis）启动、减数分裂（meiotic divisions）定型以及恢复营养生长（vegetative growth）。我们提出，由mRNA亚型与长链非编码RNA构成的可变转录组（alternative transcriptome）可塑造细胞命运转变过程中的局部基因表达模式。因此，某一基因座（locus）处转录的不同RNA的类型与比例变化，是发育不同阶段基因表达的重要调控输入因子。