Distinct roles for CTD Ser-2 and Ser-5 phosphorylation in the recruitment and allosteric activation of mammalian mRNA capping enzyme Journal Article

  

Authors:	Ho, C. K.; Shuman, S.
Article Title:	Distinct roles for CTD Ser-2 and Ser-5 phosphorylation in the recruitment and allosteric activation of mammalian mRNA capping enzyme
Abstract:	Capping is targeted to pre-mRNAs through binding of the guanylyltransferase component of the capping apparatus to the phosphorylated CTD of RNA polymerase II. We report that mammalian guanylyltransferase binds synthetic CTD peptides containing phosphoserine at either position 2 or 5 of the YSPTSPS heptad repeat. CTD peptides containing Ser-5-PO4 stimulate guanylyltransferase activity by enhancing enzyme affinity for GTP and increasing the yield of the enzyme-GMP intermediate. A CTD peptide containing Ser-2PO4 has no effect on guanylyltransferase activity. This implies an allosteric change in guanylyltransferase conformation that is specified by the position of phosphoserine in the CTD. Stimulation of guanylyltransferase increases with the number of Ser-5-phosphorylated heptads. Our results underscore how mRNA production may be regulated by the display of different CTD phosphorylation arrays during transcription elongation.
Keywords:	controlled study; protein phosphorylation; nonhuman; protein domain; mouse; animals; mice; serine; carboxy terminal sequence; transcription, genetic; enzyme activation; enzyme activity; hela cells; phosphorylation; recombinant fusion proteins; messenger rna; mammal; guanosine triphosphate; rna polymerase ii; rna transcription; phosphoserine; allosteric regulation; allosterism; phosphopeptides; rna capping; nucleotidyltransferases; chromatography, affinity; transferase; microspheres; repetitive sequences, amino acid; guanosine phosphate; humans; article
Journal Title:	Molecular Cell
Volume:	3
Issue:	3
ISSN:	1097-2765
Publisher:	Cell Press
Date Published:	1999-03-01
Start Page:	405
End Page:	411
Language:	English
DOI:	10.1016/s1097-2765(00)80468-2
PUBMED:	10198643
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0033105827&partnerID=40&md5=6fa91f2fbefa7fbb02dfe8b9f11aee63
Notes:	Article -- Export Date: 16 August 2016 -- Source: Scopus

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