The Role of mRNA Stability in the Control of Globin Gene Expression

The expression of HMGA genes is regulated by their 3′UTR

“…Database searches with these four regions showed only a weak homology of conserved region number 4 (nt 9867 ± 9976) to a pyrimidine-rich element within the 3'UTR of alphaglobin. This element protects the alpha-globin mRNA from degradation through an unknown mechanism, by protecting it against erythroid cell speci®c destabilization (Russell et al, 1997).…”

Control of human -globin mRNA stability and its impact on beta-thalassemia phenotype

“…The cis-acting determinants include the 5' m 7 Gppp cap structure, the 5' and 3' untranslated regions (UTRs), the 3' polyadenylated [poly(A)] tail and sequences in the coding region. [1][2][3][4] The closed loop structure shared by almost all eukaryotic mRNAs that link the 5' cap structure to the 3' poly(A) tail through the interaction of the cap binding protein complex with the poly(A) binding protein (PABP) contributes to mRNA stability as it protects the termini from exonuclease activity. [1][2][3] Examples of other determinants that regulate mRNA stability include AU-rich elements in the 3'UTR of some interleukin mRNAs and the iron-responsive element in the transferrin receptor mRNA, or the JNKresponse element in the 5'UTR of the interleukin-2 transcript.…”

“…[1][2][3][4] The closed loop structure shared by almost all eukaryotic mRNAs that link the 5' cap structure to the 3' poly(A) tail through the interaction of the cap binding protein complex with the poly(A) binding protein (PABP) contributes to mRNA stability as it protects the termini from exonuclease activity. [1][2][3] Examples of other determinants that regulate mRNA stability include AU-rich elements in the 3'UTR of some interleukin mRNAs and the iron-responsive element in the transferrin receptor mRNA, or the JNKresponse element in the 5'UTR of the interleukin-2 transcript. 4 Otherwise, mRNA degradation typically initiates with deadenylation of the 3' poly(A) tail followed by decapping and degradation of the mRNA body in either the 5' to 3' or the 3' to 5' direction.…”

“…In most studies, globin mRNA half-lives vary from 10 to 24 hours. 3 Several naturally occurring mutations affecting the expression of human globin genes, resulting in the clinical syndrome of thalassemia, have been described. The outcome of many of these thalassemic mutations is the inhibition of efficient mRNA transcription and/or processing, resulting in decreased mRNA levels.…”

“…Destabilization of abnormally processed mRNAs may result from mutations that affect normal splicing or block polyadenylation. 3 Mutations that introduce premature translation-termination codons (PTCs; nonControl of human b-globin mRNA stability and its impact on beta-thalassemia phenotype 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.…”