The increasing diversity of functions attributed to the SAFB family of RNA-/DNA-binding proteins.

Michael Norman,James Uney,Caroline Rivers,Youn-Bok Lee,Jalilah Idris

doi:10.1042/bcj20160649

Michael Norman, James Uney + Show 3 more

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https://doi.org/10.1042/bcj20160649

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Abstract

RNA-binding proteins play a central role in cellular metabolism by orchestrating the complex interactions of coding, structural and regulatory RNA species. The SAFB (scaffold attachment factor B) proteins (SAFB1, SAFB2 and SAFB-like transcriptional modulator, SLTM), which are highly conserved evolutionarily, were first identified on the basis of their ability to bind scaffold attachment region DNA elements, but attention has subsequently shifted to their RNA-binding and protein-protein interactions. Initial studies identified the involvement of these proteins in the cellular stress response and other aspects of gene regulation. More recently, the multifunctional capabilities of SAFB proteins have shown that they play crucial roles in DNA repair, processing of mRNA and regulatory RNA, as well as in interaction with chromatin-modifying complexes. With the advent of new techniques for identifying RNA-binding sites, enumeration of individual RNA targets has now begun. This review aims to summarise what is currently known about the functions of SAFB proteins.

Highlights

In this review, we discuss three scaffold attachment factor B (SAFB) proteins [SAFB1, SAFB2 and SAFB-like transcriptional modulator, SLTM] that bind both DNA and RNA
Using the individual nucleotide resolution cross-linking and immunoprecipitation (iCLIP) assay, we have found that SAFB1 binds to several Long non-coding RNAs (lncRNAs) transcripts (MALAT1, NEAT1, TUG1 and XIST), which have been linked to regulation of gene expression [43]
Townson et al [103] showed that overexpression of SAFB1 inhibited cell growth and markedly decreased colony formation, whereas we found that overexpression of SLTM [13] and SAFB1 causes apoptosis

Summary

Introduction

We discuss three scaffold attachment factor B (SAFB) proteins [SAFB1, SAFB2 and SAFB-like transcriptional modulator, SLTM] that bind both DNA and RNA. A high proportion of these DRBPs are involved in the regulation of transcription and processing of newly transcribed RNA, but a surprisingly high proportion is involved in DNA repair, apoptosis and the response to cellular stresses, such as heat shock. This wide range of functions applies to the SAFB family (Figure 1A). SAFB is widely expressed in vertebrates, including fish, birds, reptiles and mammals. It is found in Drosophila [2]. Such conservation over at least 500 million years of evolution is a testament to the importance that these proteins must have in cellular processes

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