Nuclear factor 90 uses an ADAR2-like binding mode to recognize specific bases in dsRNA.

Uma Jayachandran,Heather Grey,Atlanta G Cook

doi:10.1093/nar/gkv1508

Uma Jayachandran, Heather Grey + Show 1 more

Open Access

https://doi.org/10.1093/nar/gkv1508

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Abstract

Nuclear factors 90 and 45 (NF90 and NF45) form a protein complex involved in the post-transcriptional control of many genes in vertebrates. NF90 is a member of the dsRNA binding domain (dsRBD) family of proteins. RNA binding partners identified so far include elements in 3′ untranslated regions of specific mRNAs and several non-coding RNAs. In NF90, a tandem pair of dsRBDs separated by a natively unstructured segment confers dsRNA binding activity. We determined a crystal structure of the tandem dsRBDs of NF90 in complex with a synthetic dsRNA. This complex shows surprising similarity to the tandem dsRBDs from an adenosine-to-inosine editing enzyme, ADAR2 in complex with a substrate RNA. Residues involved in unusual base-specific recognition in the minor groove of dsRNA are conserved between NF90 and ADAR2. These data suggest that, like ADAR2, underlying sequences in dsRNA may influence how NF90 recognizes its target RNAs.

Highlights

Nuclear factor 90 (NF90) is a double-stranded RNA binding protein, conserved in vertebrates, which affects gene expression at transcriptional, posttranscriptional and translational levels [1,2,3]
We made use of a previous study by Rigo et al [23]. They showed that NF90/nuclear factor 45 (NF45) complexes are recruited to mRNA transcripts in cells transfected with complementary 18mer oligonucleotides uniformly modified at the 2 ribose position with fluorine (2 F) [23]
NF90long/NF45, NF90long and NF90dsRBDs show the formation of two distinct RNA– protein complexes at 1:1 and 1:2 RNA:protein (Figure 1C)

Summary

Introduction

Nuclear factor 90 (NF90) is a double-stranded RNA (dsRNA) binding protein, conserved in vertebrates, which affects gene expression at transcriptional, posttranscriptional and translational levels [1,2,3]. NF90 (and its brain- and testes-specific paralogue, spermatid perinuclear RNA binding protein, SPNR [12]) consists of three structured domains followed by a C-terminal region that is predicted to be natively unstructured (Figure 1A). Downstream of the DZF domain there is a nuclear localization signal (NLS) followed by a tandem pair of double stranded RNA binding domains (dsRBDs) separated by a 52 amino acid linker sequence that is predicted to be natively unstructured (Figure 1A)

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