Brain-specific promoter and polyadenylation sites of the beta-adducin pre-mRNA generate an unusually long 3'-UTR.
Adducins are a family of membrane skeleton proteins composed of alpha-, beta- and gamma-subunits that promote actin and spectrin association in erythrocytes. The alpha- and gamma-subunits are expressed ubiquitously, while the beta-subunit is found in brain and erythropoietic tissues. The brain beta-adducin protein is similar in size to that of spleen, but the mRNA transcript is a brain-specific one that has not been yet characterized, having an estimated length of 8-9 kb instead of the 3-4 kb of spleen mRNA. Here, we show the molecular basis for these differences by determining the structure of the brain-specific beta-adducin transcript in rats, mice and humans. We identified a brain-specific promoter in rodents that, apparently, was not conserved in humans. In addition, we present evidence that the brain-mRNAs are formed by a common mechanism consisting in the tissue-specific use of alternative polyadenylation sites generating unusually long 3'-untranslated region of up to 6.6 kb. This hypothesis is supported by the presence of highly-conserved regions flanking the brain-specific polyadenylation site that suggest the involvement of these sequences in the translational regulation, stability and/or subcellular localization of the beta-adducin transcript in the brain.
Costessi
Luisa
L
International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Devescovi
Giulia
G
Baralle
Francisco E
FE
Muro
Andrés F
AF
D020413:3' Untranslated Regions / Q000737:chemistry*; D020121:5' Untranslated Regions / Q000737:chemistry; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002148:Calmodulin-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D017124:Conserved Sequence; D005091:Exons; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D026723:Polyadenylation; D011401:Promoter Regions, Genetic; D012322:RNA Precursors / Q000096:biosynthesis / Q000737:chemistry*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000378:metabolism; D000099291:Adducins
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D002148:Calmodulin-Binding Proteins; D012322:RNA Precursors; D012333:RNA, Messenger; D000099291:Adducins