Linked Life Data

16807757

Source:http://linkedlifedata.com/resource/pubmed/id/16807757

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-9-19
pubmed:abstractText
In an attempt both to catalogue 3' regulatory region (3' RR)-mediated disease and to improve our understanding of the structure and function of the 3' RR, we have performed a systematic analysis of disease-associated variants in the 3' RRs of human protein-coding genes. We have previously analysed the variants that have occurred in two specific domains/motifs of the 3' untranslated region (3' UTR) as well as in the 3' flanking region. Here we have focused upon 83 known variants within the upstream sequence (USS; between the translational termination codon and the upstream core polyadenylation signal sequence) of the 3' UTR. To place these variants in their proper context, we first performed a comprehensive survey of known cis-regulatory elements within the USS and the mechanisms by which they effect post-transcriptional gene regulation. Although this survey supports the view that RNA regulatory elements function within the context of specific secondary structures, there are no general rules governing how secondary structure might exert its influence. We have therefore addressed this question by systematically evaluating both functional and non-functional (based upon in vitro reporter gene and/or electrophoretic mobility shift assay data) USS variant-containing sequences against known cis-regulatory motifs within the context of predicted RNA secondary structures. This has allowed us not only to establish a reliable and objective means to perform secondary structure prediction but also to identify consistent patterns of secondary structural change that could potentiate the discrimination of functional USS variants from their non-functional counterparts. The resulting rules were then used to infer potential functionality in the case of some of the remaining functionally uncharacterized USS variants, from their predicted secondary structures. This not only led us to identify further patterns of secondary structural change but also several potential novel cis-regulatory motifs within the 3' UTRs studied.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0340-6717
pubmed:author
pubmed:issnType
Print
pubmed:volume
120
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
301-33
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
A systematic analysis of disease-associated variants in the 3' regulatory regions of human protein-coding genes II: the importance of mRNA secondary structure in assessing the functionality of 3' UTR variants.
pubmed:affiliation
INSERM, U613, 29220, Brest, France. Jian-Min.Chen@univ-brest.fr
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't