PIPPin is a brain-specific protein that contains a cold-shock domain and binds specifically to H1 degrees and H3.3 mRNAs.
During maturation of mammalian brain, variants of both linker (i.e. H1 degrees) and core (i.e. H3.3) histone proteins accumulate in nerve cells. As the concentration of the corresponding transcripts decreases, in postmitotic cells, even if the genes are actively transcribed, it is likely that regulation of variant histone expression has relevant post-transcriptional components and that cellular factors affect histone mRNA stability and/or translation. Here we report that PIPPin, a protein that is highly enriched in the rat brain and contains a cold-shock domain, binds with high specificity to the transcripts that encode H1 degrees and H3.3 histone variants. Both mRNAs are bound through the very end of their 3'-untranslated region that encompasses the polyadenylation signal. Although PIPPin is present both in the cytoplasm and the nucleus of nerve cells, PIPPin-RNA complexes can be obtained only from nuclear extracts. The results of two-dimensional electrophoretic analysis suggest that a relevant proportion of nuclear PIPPin is more acidic than expected, thus suggesting that its RNA binding activity might be modulated by post-translational modifications, such as phosphorylation.
Nastasi
T
T
Dipartimento di Biologia Cellulare e dello Sviluppo "A. Monroy," viale delle Scienze, Parco d'Orleans, 90128 Palermo, Italy.
Scaturro
M
M
Bellafiore
M
M
Raimondi
L
L
Beccari
S
S
Cestelli
A
A
di Liegro
I
I
D020413:3' Untranslated Regions; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001923:Brain Chemistry; D002467:Cell Nucleus / Q000737:chemistry; D002478:Cells, Cultured; D003080:Cold Temperature; D005260:Female; D006657:Histones / Q000235:genetics*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
D020413:3' Untranslated Regions; C097845:Csdc2 protein, rat; D006657:Histones; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins