Structural insights into Gemin5-guided selection of pre-snRNAs for snRNP assembly.

Abstract:

:In cytoplasm, the survival of motor neuron (SMN) complex delivers pre-small nuclear RNAs (pre-snRNAs) to the heptameric Sm ring for the assembly of the ring complex on pre-snRNAs at the conserved Sm site [A(U)4-6G]. Gemin5, a WD40 protein component of the SMN complex, is responsible for recognizing pre-snRNAs. In addition, Gemin5 has been reported to specifically bind to the m7G cap. In this study, we show that the WD40 domain of Gemin5 is both necessary and sufficient for binding the Sm site of pre-snRNAs by isothermal titration calorimetry (ITC) and mutagenesis assays. We further determined the crystal structures of the WD40 domain of Gemin5 in complex with the Sm site or m7G cap of pre-snRNA, which reveal that the WD40 domain of Gemin5 recognizes the Sm site and m7G cap of pre-snRNAs via two distinct binding sites by respective base-specific interactions. In addition, we also uncovered a novel role of Gemin5 in escorting the truncated forms of U1 pre-snRNAs for proper disposal. Overall, the elucidated Gemin5 structures will contribute to a better understanding of Gemin5 in small nuclear ribonucleic protein (snRNP) biogenesis as well as, potentially, other cellular activities.

journal_name

Genes Dev

journal_title

Genes & development

authors

Xu C,Ishikawa H,Izumikawa K,Li L,He H,Nobe Y,Yamauchi Y,Shahjee HM,Wu XH,Yu YT,Isobe T,Takahashi N,Min J

doi

10.1101/gad.288340.116

subject

Has Abstract

pub_date

2016-11-01 00:00:00

pages

2376-2390

issue

21

eissn

0890-9369

issn

1549-5477

pii

gad.288340.116

journal_volume

30

pub_type

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