An alternative transcriptome shapes cell fate transitions in yeast (TSS-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剪接变体（alternative mRNA isoforms）与长链非编码RNA（long noncoding RNA，lncRNA）在转录组中占比可观，并在细胞命运编程过程中发挥关键功能。此类转录本通常起始于编码基因启动子上游的可变转录起始位点（alternative transcription start site, TSS），可通过转录偶联的染色质改变以顺式调控方式影响基因表达。目前学界对可变顺式作用RNA的转录如何、何时以及在何处调控局部基因表达的机制仍了解有限。本研究采用高分辨率定量分析方法，针对酵母中三种不同细胞命运转变过程中的可变TSS及转录终止位点（transcript end site, TES）使用情况展开研究：分别为进入配子发生阶段、获得减数分裂定向以及恢复营养生长。我们提出，由mRNA剪接变体与lncRNA组成的可变转录组，可在细胞命运转变过程中塑造局部基因的表达模式。因此，基因座处转录产生的不同RNA的类型与比例变化，是发育不同阶段基因表达调控的重要输入因素。