Signal Manager :: View

r1={au,ua,gc,cg,gu,ug}
0...1 mmmm p1=ggyyy u hhuh a r1~p1 mm 0...3

Metazoan histone 3'-UTR mRNAs, lacking a polyA tail, contain a highly conserved stem-loop structure with a six base stem and a four base loop (HSL3). This stem-loop structure plays a different role in the nucleus and in the cytoplasm. In the nucleus, it is involved in pre-mRNA processing and nucleocytoplasmic transport, whereas in the cytoplasm it enhances translation efficiency and regulates histone mRNA stability. The trans-acting factor which interacts with the 3'-UTR hairpin structure of histone mRNAs is a 31 kDa stem-loop binding protein in mammals (SLBP) present both in nuclei and polyribosomes. In mammals in addition to SLBP, which also stimulate translation, histone mRNA processing involves additional factors including: i) the U7 snRNP, which binds a purine-rich element 10-20 nt downstream of the stem-loop sequence (Histone Downstream Element, HDE);  ii) a 3'->5' exonuclease 3'hExo, which can bind the 3' side of HSL3 both alone and simultaneously with SLBP; and iii) ZFP100 a 100kDa zinc-finger protein recognizing the complex between HSL3 and SLBP (Dominski et al., 2007).

In all histone mRNAs analyzed so far no G has been observed in the four base loop. In all metazoan except C. elegans , there are two invariant urydines in the first and third base of the loop. In C.elegans the first base of the loop is C. Either 5' and 3' flanking sequences are necessary for high affinity binding of SLBP. The 5' flanking sequence consensus is CCAAA and the 3' flanking sequence consensus is ACCCA or ACCA with cleavage occuring after the A. The histone 3'-UTR hairpin structure is peculiar in that the bases of the stem are conserved unlike most functional hairpin motifs where conserved bases are found in single stranded loop regions only. The sequence of the stem and flanking sequences are critical for binding of the SLBP.