Solution structure of the U11-48K CHHC zinc-finger domain that specifically binds the 5' splice site of U12-type introns.
The formation of stable 18S U11/U12 di-snRNPs before their association with the pre-mRNA is a characteristic feature of the minor spliceosome. During the spliceosomal assembly, the 18S snRNP binds cooperatively to the introns' 5' splice and branch point site. The molecular basis for this recognition is still unknown. Here, we report the solution structure of the U11-48K CHHC Zn finger, a domain unique to the minor spliceosome. The CHHC Zn-finger structure revealed an unexpected similarity to the TFIIIA domains, with distinct features originating from the type and separation of the zinc-coordinating residues. We show that this domain specifically binds the 5' splice site sequence of U12-type introns when base paired to U11 snRNA in vitro and hence may contribute to the U12 intron recognition. We propose a model in which the U11-48K Zn finger stabilizes U11-5' splice site base pairing and thus plays an important role during the minor spliceosome assembly.
Tidow
Henning
H
MRC Centre for Protein Engineering, Hills Road, Cambridge CB20QH, United Kingdom. tidow@mrc-lmb.cam.ac.uk
Andreeva
Antonina
A
Rutherford
Trevor J
TJ
Fersht
Alan R
AR
D000595:Amino Acid Sequence; D020029:Base Pairing / Q000502:physiology; D006801:Humans; D007438:Introns; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D022821:RNA Splice Sites / Q000502:physiology; D020871:RNA Stability / Q000502:physiology; D012342:RNA, Small Nuclear / Q000235:genetics* / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D012996:Solutions; D017381:Spliceosomes / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D016335:Zinc Fingers / Q000502:physiology
D022821:RNA Splice Sites; D012342:RNA, Small Nuclear; D017411:Ribonucleoproteins, Small Nuclear; D012996:Solutions; C552126:U11-U12 small nuclear ribonucleoprotein; C096986:U12 small nuclear RNA