The RRM-type RNA-binding protein Mei2 is a master regulator of meiosis in fission yeast where it stabilizes meiosis-specific mRNAs by blocking their destruction. mediated by Wis1 MAPKK and Sty1 MAPK is critical for this stress response. Sty1 phosphorylates Lsk1 the catalytic subunit of CTDK-I. Furthermore a feedback loop stemming from activated Mei2 to Win1 and Wis4 MAPKKKs operates in this pathway and eventually enhances CTD Ser-2 phosphorylation and transcription. Hence in addition to starting meiosis Mei2 functions to reinforce the commitment to it once cells have entered this process. This study also demonstrates clearly that the stress-responsive MAP kinase pathway can modulates gene expression through phosphorylation of Pol II CTD. Author Summary Hundreds of genes are newly expressed during meiosis a process to form gametes and the control of meiosis-specific gene expression is not simple. The master regulator of meiosis in Olprinone Hydrochloride fission yeast Mei2 blocks an RNA destruction system that selectively degrades meiosis-specific mRNAs highlighting the importance of post-transcriptional control in meiotic gene expression. Here we present another example of unforeseen regulation for meiosis. Ste11 is a key transcription factor responsible for the early meiotic gene expression in fission yeast. The gene is transcribed robustly only when serine-2 residues on the C-terminal Olprinone Hydrochloride domain (CTD Ser-2) of RNA polymerase II are phosphorylated. We show that the stress-responsive MAP kinase cascade transmits the environmental signal to stimulate CTD Ser-2 phosphorylation. Sty1 MAP kinase appears to phosphorylate and activate the catalytic subunit of CTDK-I which Olprinone Hydrochloride in turn phosphorylates CTD Ser-2. We demonstrate further that Mei2 expression of which depends on Ste11 can activate the MAP kinase cascade forming a feedback loop. Thus we clarify here three important issues in cellular development: the physiological role of CTD Ser-2 phosphorylation the molecular function of the stress-responsive MAP kinase pathway and the presence of positive feedback that reinforces the commitment to meiosis. Introduction The cell cycle programs for mitosis and meiosis appear to be strictly segregated from each other Olprinone Hydrochloride although they are likely to have molecular systems in keeping. Analyses in lower eukaryotes show that factors needed specifically for meiosis generated through the transcriptional activation of meiosis-specific genes are mainly in charge of the segregation of the two procedures [1] [2]. Furthermore we’ve reported previously in fission candida that meiosis-specific mRNAs transcribed at the CCNA1 incorrect time through the mitotic cell routine are eliminated selectively by Olprinone Hydrochloride nuclear exosomes therefore preventing the unacceptable manifestation from the meiotic system in mitotic cells [3] [4]. The get better at meiotic regulator in fission candida Mei2 an RNA-binding proteins with three RRM domains [5]-[7] suppresses the function of the selective removal program by sequestering an essential component Mmi1 which can be an RNA-binding proteins from the YTH family members [3]. Mei2 therefore ensures full manifestation of meiosis-specific genes and facilitates execution from the meiotic system (evaluated in [8]). Nonetheless it can be unlikely how the function of Mei2 in meiosis can be confined towards the tethering of Mmi1 as the artificial inactivation of Mmi1 will not induce the entire meiotic system whereas the experimental induction from the activated type of Mei2 will therefore [3] [6]. The systems and pathways where Mei2 promotes the complete meiotic system can be therefore a topic of considerable curiosity. To identify feasible upstream or downstream effectors of Mei2 we devised a fresh screening program and discovered that a subunit of CTDK-I which really is a CDK-like kinase complicated that phosphorylates the C-terminal replicate domain of the biggest subunit of RNA polymerase II (Pol II CTD) [9] [10] could genetically connect to Mei2. More particularly the phosphorylation of Pol II CTD by CTDK-I was found to influence the expression of gene. Pol II CTD serves as a binding scaffold for a variety of nuclear factors and its phosphorylation status has been implicated in regulation of an ever-increasing number of functions necessary to execute complex transcriptional processes [9] [10]. Our aforementioned findings indicate that the phosphorylation of Ser-2 residues on Pol II CTD in fission yeast is unique in that it is required mainly for the meiotic program via the activation of.