title: Control of human beta-globin mRNA stability and its impact on beta-thalassemia phenotype.
abstract: Messenger RNA (mRNA) stability is a critical determinant that affects gene expression. Many pathways have evolved to modulate mRNA stability in response to developmental, physiological and/or environmental stimuli. Eukaryotic mRNAs have a considerable range of half-lives, from as short as a few minutes to as long as several days. Human globin mRNAs constitute an example of highly stable mRNAs. However, a wide variety of naturally occurring mutations that result in the clinical syndrome of thalassemia can trigger accelerated mRNA decay thus controlling mRNA quality prior to translation. Distinct surveillance mechanisms have been described as being targeted for specific defective globin mRNAs. Here, we review mRNA stability mechanisms implicated in the control of β-globin gene expression and the surveillance pathways that prevent translation of aberrant β-globin mRNAs. In addition, we emphasize the importance of these pathways in modulating the severity of the β-thalassemia phenotype.
authors.affiliation: Departamento de Genética, Instituto Nacional de Saúde Dr. Ricardo Jorge, Av. Padre Cruz, 1649-016 Lisboa, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Peixeiro
authors.forename: Ana Luísa
authors.initials: AL
authors.lastname: Silva
authors.forename: Luísa
authors.initials: L
authors.lastname: Romão
mesh_terms: D005786:Gene Expression Regulation; D006801:Humans; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D055544:beta-Globins / Q000235:genetics* / Q000378:metabolism*; D017086:beta-Thalassemia / Q000235:genetics* / Q000503:physiopathology*
chemical_list: D012333:RNA, Messenger; D012261:Ribonucleoproteins; D055544:beta-Globins; C026452:messenger ribonucleoprotein