Disease relevance of SRP9

• Monomeric scAlu and nascent dimeric Alu RNAs induced by adenovirus are assembled into SRP9/14-containing RNPs in HeLa cells [1].

High impact information on SRP9

• The Alu domain of the mammalian signal recognition particle (SRP) comprises the heterodimer of proteins SRP9 and SRP14 bound to the 5' and 3' terminal sequences of SRP RNA [2].
• Loss of Alu right monomer affinity for SRP9/14 is associated with scAlu RNA production from Alu elements in vivo [3].
• RNase protection and filter binding experiments have shown that binding of SRP9/14 to SRP RNA depends solely on sequences located in a domain of SRP RNA that is strongly homologous to the Alu family of repetitive DNA sequences [4].
• In addition, the use of hydroxyl radicals, as RNA-cleaving reagents, has revealed four distinct regions in this domain that are in close contact with SRP9/14 [4].
• These data are consistent with nascent SRP and/or Alu RNAs first binding to SRP 9/14-kDa protein heterodimer, followed by the removal of extra sequence on the 3' end and then the addition of one adenylic acid residue in the nucleus, before transport into the cytoplasm [5].

Biological context of SRP9

• Our findings that there is a large excess of SRP9/14 in primate cells and that Alu RNAs are bound to SRP9/14 in vivo suggest that this heterodimeric protein may play additional roles in the translational control of gene expression and/or Alu transcript metabolism [6].
• Mutations disrupting base pairing interfere with folding of the Alu portion of the SRP RNA as monitored by probing the RNA structure and the binding of the protein SRP9/14 [7].
• Both transgenically expressed npcRNAs formed RNP complexes with poly(A) binding protein and the heterodimer SRP9/14, as does BC200 RNA in human [8].

Anatomical context of SRP9

• Kd values for three Alu-homologous scRNAs were determined using Alu RBP (SRP9/14) purified from HeLa cells [9].
• This region of 7SL RNA together with 9- and 14-kDa polypeptides (SRP9/14) regulates translational elongation of ribosomes engaged by SRP [9].

Physical interactions of SRP9

• The SRP9 protein binds only as dimer with SRP14 protein to the Alu domain of 7SL RNA to form a subdomain that, in SRP, is functional in translation arrest [10].

Other interactions of SRP9

• Although SRP9 proteins are the same size in both rodent and primate cells, SRP14 subunits are generally larger in primate cells [6].
• Heterodimer SRP9/14 is an integral part of the neural BC200 RNP in primate brain [10].

References