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Title: Transcription of lncRNA prt , clustered prt RNA sites for Mmi1 binding, and RNA polymerase II CTD phospho-sites govern the repression of pho1 gene expression under phosphate-replete conditions in fission yeast

Journal Article · · RNA
 [1];  [2];  [1];  [1];  [2]
  1. Memorial Sloan Kettering Cancer Center, New York, NY (United States). Sloan Kettering Institute
  2. Cornell Univ., Ithaca, NY (United States). Weill Medical College

Expression of fission yeast Pho1 acid phosphatase is repressed during growth in phosphate-rich medium. Repression is mediated by transcription of the prt locus upstream of pho1 to produce a long noncoding (lnc) prt RNA. Repression is also governed by RNA polymerase II CTD phosphorylation status, whereby inability to place a Ser7-PO4 mark (as in S7A) derepresses Pho1 expression, and inability to place a Thr4-PO4 mark (as in T4A) hyper-represses Pho1 in phosphate replete cells. Here we find that basal pho1 expression from the prt–pho1 locus is inversely correlated with the activity of the prt promoter, which resides in a 110-nucleotide DNA segment preceding the prt transcription start site. CTD mutations S7A and T4A had no effect on the activity of the prt promoter or the pho1 promoter, suggesting that S7A and T4A affect post-initiation events in prt lncRNA synthesis that make it less and more repressive of pho1, respectively. prt lncRNA contains clusters of DSR (determinant of selective removal) sequences recognized by the YTH-domain-containing protein Mmi1. Altering the nucleobase sequence of two DSR clusters in the prt lncRNA caused hyper-repression of pho1 in phosphate replete cells, concomitant with increased levels of the prt transcript. The isolated Mmi1 YTH domain binds to RNAs with single or tandem DSR elements, to the latter in a noncooperative fashion. We report the 1.75 Å crystal structure of the Mmi1 YTH domain and provide evidence that Mmi1 recognizes DSR RNA via a binding mode distinct from that of structurally homologous YTH proteins that recognize m6A-modified RNA.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1274769
Journal Information:
RNA, Vol. 22, Issue 7; ISSN 1355-8382
Publisher:
Cambridge University PressCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 42 works
Citation information provided by
Web of Science

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Cited By (16)

The pol II CTD: new twists in the tail journal September 2016
NR2C2-uORF targeting UCA1-miR-627-5p-NR2C2 feedback loop to regulate the malignant behaviors of glioma cells journal December 2018
A conserved dimer interface connects ERH and YTH family proteins to promote gene silencing journal January 2019
RNA polymerase II CTD interactome with 3′ processing and termination factors in fission yeast and its impact on phosphate homeostasis journal October 2018
A low-complexity region in the YTH domain protein Mmi1 enhances RNA binding journal April 2018
Inositol pyrophosphates impact phosphate homeostasis via modulation of RNA 3′ processing and transcription termination journal July 2019
mmi1 and rep2 mRNAs are novel RNA targets of the Mei2 RNA-binding protein during early meiosis in Schizosaccharomyces pombe journal September 2018
Distribution, Characteristics, and Regulatory Potential of Long Noncoding RNAs in Brown-Rot Fungi journal May 2019
Meiotic gene silencing complex MTREC/NURS recruits the nuclear exosome to YTH-RNA-binding protein Mmi1 journal February 2020
Selective termination of lnc RNA transcription promotes heterochromatin silencing and cell differentiation journal July 2017
meiRNA, A Polyvalent Player in Fission Yeast Meiosis journal September 2019
YTH-RNA-binding protein prevents deleterious expression of meiotic proteins by tethering their mRNAs to nuclear foci journal February 2018
ketu mutant mice uncover an essential meiotic function for the ancient RNA helicase YTHDC2 posted_content December 2017
Inositol pyrophosphates impact phosphate homeostasis via modulation of RNA 3’ processing and transcription termination posted_content May 2019
Meiotic gene silencing complex MTREC/NURS recruits the nuclear exosome to YTH-RNA-binding protein Mmi1 text January 2020
Distinctive structural basis for DNA recognition by the fission yeast Zn2Cys6 transcription factor Pho7 and its role in phosphate homeostasis journal September 2018