A HUMAN ALU RNA-BINDING PROTEIN WHOSE EXPRESSION IS ASSOCIATED WITH ACCUMULATION OF SMALL CYTOPLASMIC ALU RNA

Human Alu sequences are short interspersed DNA elements which have bee n greatly amplified by retrotransposition. Although initially derived from the 7SL RNA component of signal recognition particle (SRP), the A lu sequence has evolved into a dominant transposon while retaining a s pecific secondary structure found in 7SL RNA. We previously characteri zed a set of Alu sequences which are expressed as small cytoplasmic RN As and isolated a protein that binds to these transcripts. Here we rep ort that biochemical purification of this protein revealed it as the h uman homolog of the SRP 14 polypeptide which binds the Alu-homologous region of 7SL RNA. The human cDNA predicts an alanine-rich C-terminal tail translated from a trinucleotide repeat not found in the rodent ho molog, which accounts for why the human protein-RNA complex migrates m ore slowly than its rodent counterpart in RNA mobility shift assays. T he human Alu RNA-binding protein (RBP) is expressed after transfection of this cDNA into mouse cells. Expression of human RBP in rodent x hu man Somatic cell hybrids is associated with substantial increase in en dogenous small cytoplasmic Alu and scB1 transcripts but not other smal l RNAs. These studies provide evidence that this RBP associates with A la transcripts in vivo and affects their metabolism and suggests a rol e for Alu transcripts in translation in an SRP-like manner. Analysis o f hybrid lines indicated that the Alu RBP gene maps to human chromosom e 15q22, which was confirmed by Southern blotting. The possibility tha t the primate-specific structure of this protein may have contributed to Alu evolution is considered.