Enhancer of rudimentary homologue interacts with scaffold attachment factor B at the nuclear matrix to regulate SR protein phosphorylation

Scaffold attachment factor B1 ( SAFB 1) is an integral component of the nuclear matrix of vertebrate cells. It binds to DNA on scaffold/matrix attachment region elements, as well as to RNA and a multitude of different proteins, affecting basic cellular activities such as transcription, splicing and DNA damage repair. In the present study, we show that enhancer of rudimentary homologue ( ERH ) is a new molecular partner of SAFB 1 and its 70% homologous paralogue, scaffold attachment factor B2 ( SAFB 2). ERH interacts directly in the nucleus with the C‐terminal Arg‐Gly‐rich region of SAFB 1/2 and co‐localizes with it in the insoluble nuclear fraction. ERH , a small ubiquitous protein with striking homology among species and a unique structure, has also been implicated in fundamental cellular mechanisms. Our functional analyses suggest that the SAFB / ERH interaction does not affect SAFB 1/2 function in transcription (e.g. as oestrogen receptor α co‐repressors), although it reverses the inhibition exerted by SAFB 1/2 on the splicing kinase SR protein kinase 1 ( SRPK 1), which also binds on the C‐terminus of SAFB 1/2. Accordingly, ERH silencing decreases lamin B receptor and SR protein phosphorylation, which are major SRPK 1 substrates, further substantiating the role of SAFB 1 and SAFB 2 in the co‐ordination of nuclear function.