Marayati Bahjat Fadi, Hoskins Victoria, Boger Robert W, Tucker James F, Fishman Emily S, Bray Andrew S, Zhang Ke
Department of Biology and Center for Molecular Communication and Signaling, Wake Forest University, Winston-Salem, North Carolina 27106, USA.
Program of Human Genetics, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
RNA. 2016 Sep;22(9):1349-59. doi: 10.1261/rna.055608.115. Epub 2016 Jun 30.
Meiosis is a highly regulated process by which genetic information is transmitted through sexual reproduction. It encompasses unique mechanisms that do not occur in vegetative cells, producing a distinct, well-regulated meiotic transcriptome. During vegetative growth, many meiotic genes are constitutively transcribed, but most of the resulting mRNAs are rapidly eliminated by the Mmi1-MTREC (Mtl1-Red1 core) complex. While Mmi1-MTREC targets premature meiotic RNAs for degradation by the nuclear 3'-5' exoribonuclease exosome during mitotic growth, its role in meiotic gene expression during meiosis is not known. Here, we report that Red5, an essential MTREC component, interacts with pFal1, an ortholog of eukaryotic translation initiation factor eIF4aIII in the fission yeast Schizosaccharomyces pombe In mammals, together with MAGO (Mnh1), Rnps1, and Y14, elF4AIII (pFal1) forms the core of the exon junction complex (EJC), which is essential for transcriptional surveillance and localization of mature mRNAs. In fission yeast, two EJC orthologs, pFal1 and Mnh1, are functionally connected with MTREC, specifically in the process of meiotic gene expression during meiosis. Although pFal1 interacts with Mnh1, Y14, and Rnps1, its association with Mnh1 is not disrupted upon loss of Y14 or Rnps1. Mutations of Red1, Red5, pFal1, or Mnh1 produce severe meiotic defects; the abundance of meiotic transcripts during meiosis decreases; and mRNA maturation processes such as splicing are impaired. Since studying meiosis in mammalian germline cells is difficult, our findings in fission yeast may help to define the general mechanisms involved in accurate meiotic gene expression in higher eukaryotes.
减数分裂是一个受到高度调控的过程，通过这个过程，遗传信息通过有性生殖得以传递。它包含了在营养细胞中不会出现的独特机制，从而产生一个独特的、调控良好的减数分裂转录组。在营养生长过程中，许多减数分裂基因会持续转录，但产生的大多数mRNA会被Mmi1 - MTREC（Mtl1 - Red1核心）复合体迅速清除。虽然Mmi1 - MTREC在有丝分裂生长过程中会将过早的减数分裂RNA靶向细胞核3'-5'外切核糖核酸酶外泌体进行降解，但其在减数分裂过程中对减数分裂基因表达的作用尚不清楚。在此，我们报道Red5是MTREC的一个必需组分，它与粟酒裂殖酵母中真核翻译起始因子eIF4aIII的直系同源物pFal1相互作用。在哺乳动物中，eIF4AIII（pFal1）与MAGO（Mnh1）、Rnps1和Y14一起形成外显子连接复合体（EJC）的核心，这对于转录监测和成熟mRNA的定位至关重要。在裂殖酵母中，两个EJC直系同源物pFal1和Mnh1在功能上与MTREC相连，特别是在减数分裂过程中减数分裂基因表达的过程中。虽然pFal1与Mnh1、Y14和Rnps1相互作用，但其与Mnh1的结合在Y14或Rnps1缺失时不会被破坏。Red1、Red5、pFal1或Mnh1的突变会产生严重的减数分裂缺陷；减数分裂过程中减数分裂转录本的丰度降低；并且诸如剪接等mRNA成熟过程会受到损害。由于在哺乳动物生殖系细胞中研究减数分裂很困难，我们在裂殖酵母中的发现可能有助于确定高等真核生物中准确的减数分裂基因表达所涉及的一般机制。
