Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2002-6-26
pubmed:abstractText
The 3' ends of nearly all eukaryotic pre-mRNAs undergo cleavage and polyadenylation, thereby acquiring a poly(A) tail added by the enzyme poly(A) polymerase (PAP). Two well-characterized examples of regulated poly(A) tail addition in the nucleus consist of spliceosomal proteins, either the U1A or U170K proteins, binding to the pre-mRNA and inhibiting PAP via their PAP regulatory domains (PRDs). These two proteins are the only known examples of this type of gene regulation. On the basis of sequence comparisons, it was predicted that many other proteins, including some members of the SR family of splicing proteins, contain functional PRDs. Here we demonstrate that the putative PRDs found in the SR domains of the SR proteins SRP75 and U2AF65, via fusion to a heterologous MS2 RNA binding protein, specifically and efficiently inhibit PAP in vitro and pre-mRNA polyadenylation in vitro and in vivo. A similar region from the SR domain of SRP40 does not exhibit these activities, indicating that this is not a general property of SR domains. We find that the polyadenylation- and PAP-inhibitory activity of a given polypeptide can be accurately predicted based on sequence similarity to known PRDs and can be measured even if the polypeptides' RNA target is unknown. Our results also indicate that PRDs function as part of a network of interactions within the pre-mRNA processing complex and suggest that this type of regulation will be more widespread than previously thought.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
318
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1189-206
pubmed:dateRevised
2011-9-28
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Identification of new poly(A) polymerase-inhibitory proteins capable of regulating pre-mRNA polyadenylation.
pubmed:affiliation
Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't