Abstract

An unusal subgroup of RRM domains (PFAM:PF00076) termed UHMs (U2AF Homology Motifs) have been found to have no (or weak) RNA-binding activity (Kielkopf et al., 2004). Instead of RNA, UHMs appear to bind to short induced fit protein elements. The known UHM Ligand Motifs (ULMs) show a typical signature of a short positively charged run preceding a Trp-Asp pair (although the Asp is not always conserved.) ULM sequences with important functions in mRNA processing were found in the constitutive splicing factors U2AF65, SF1 and SAP155. The structure of the U2AF65-ULM reveals a larger induced fit module than the signature motif (Kielkopf et al., 2001). It is recognized by the UHM in U2AF35 with low nanomolar affinity and mediates the heterodimerization of these two proteins, which is crucial for U2 snRNP recruitment in early splicing initiation. The SF1 ULM is used for recruitment to the branch point sequence by binding to the U2AF65-UHM (Selenko et al., 2003). ATP-dependent rearrangements of the snRNPs cause the SF1-ULM to be replaced by ULMs in SAP155 later in the splicing process (Thickman et al., 2006). Thus, the UHM-ULM interactions known so far all mediate essential interactions in the splicing process.