U7 snRNP-specific Lsm11 protein: dual binding contacts with the 100 kDa zinc finger processing factor (ZFP100) and a ZFP100-independent function in histone RNA 3' end processing.
The 3' cleavage generating non-polyadenylated animal histone mRNAs depends on the base pairing between U7 snRNA and a conserved histone pre-mRNA downstream element. This interaction is enhanced by a 100 kDa zinc finger protein (ZFP100) that forms a bridge between an RNA hairpin element upstream of the processing site and the U7 small nuclear ribonucleoprotein (snRNP). The N-terminus of Lsm11, a U7-specific Sm-like protein, was shown to be crucial for histone RNA processing and to bind ZFP100. By further analysing these two functions of Lsm11, we find that Lsm11 and ZFP100 can undergo two interactions, i.e. between the Lsm11 N-terminus and the zinc finger repeats of ZFP100, and between the N-terminus of ZFP100 and the Sm domain of Lsm11, respectively. Both interactions are not specific for the two proteins in vitro, but the second interaction is sufficient for a specific recognition of the U7 snRNP by ZFP100 in cell extracts. Furthermore, clustered point mutations in three phylogenetically conserved regions of the Lsm11 N-terminus impair or abolish histone RNA processing. As these mutations have no effect on the two interactions with ZFP100, these protein regions must play other roles in histone RNA processing, e.g. by contacting the pre-mRNA or additional processing factors.
Azzouz
Teldja N
TN
Institute of Cell Biology, University of Bern Baltzerstrasse 4, 3012 Bern, Switzerland.
Gruber
Andreas
A
Schümperli
Daniel
D
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D009154:Mutation; D017434:Protein Structure, Tertiary; D026721:RNA 3' End Processing; D016601:RNA-Binding Proteins; D020885:Ribonucleoprotein, U7 Small Nuclear / Q000378:metabolism*; D017411:Ribonucleoproteins, Small Nuclear / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D006657:Histones; C477938:Lsm11 protein, mouse; D016601:RNA-Binding Proteins; D020885:Ribonucleoprotein, U7 Small Nuclear; D017411:Ribonucleoproteins, Small Nuclear; C095988:ZNF473 protein, human