Biomedical subjects

J Sarrowa

Publications and source records attributed to J Sarrowa.

2 recordsLinked to original sources

PubMed1997

The decline in human Alu retroposition was accompanied by an asymmetric decrease in SRP9/14 binding to dimeric Alu RNA and increased expression of small cytoplasmic Alu RNA.

Alu interspersed elements are inserted into the genome by a retroposition process that occurs via dimeric Alu RNA and causes genetic disorders in humans. Alu RNA is labile and can be diverted to a stable left monomer transcript known as small cytoplasmic Alu (scAlu) RNA by RNA 3' processing, although the relationship between Alu RNA stability, scAlu RNA production, and retroposition has been unknown. In vivo, Alu and scAlu transcripts interact with the Alu RNA-binding subunit of signal recognition particle (SRP) known as SRP9/14. We examined RNAs corresponding to Alu sequences that were differentially active during primate evolution, as well as an Alu RNA sequence that is currently active in humans. Mutations that accompanied Alu RNA evolution led to changes in a conserved structural motif also found in SRP RNAs that are associated with thermodynamic destabilization and decreased affinity of the Alu right monomer for SRP9/14. In contrast to the right monomer, the Alu left monomer maintained structural integrity and high affinity for SRP9/14, indicating that scAlu RNA has been under selection during human evolution. Loss of Alu right monomer affinity for SRP9/14 is associated with scAlu RNA production from Alu elements in vivo. Moreover, the loss in affinity coincided with decreased rates of Alu amplification during primate evolution. This indicates that stability of the Alu right monomer is a critical determinant of Alu retroposition. These results provide insight into Alu mobility and evolution and into how retroposons may interact with host proteins during genome evolution.

3T3 Cells↗

PubMed1993

Primary structure of Xenopus laevis S10, a ribosomal protein that cross-reacts with antibodies to immunoglobulin light chains.

Screening of a cDNA expression library from Xenopus laevis splenocytes with purified antibodies to Xenopus immunoglobulin light chains unexpectedly led to the isolation of a clone with an insert whose deduced amino acid sequence is similar to that of a segment of a protein, S10, from the small (40S) subunit of rat ribosomes. A clone containing an insert encoding the corresponding complete protein was isolated from another cDNA library by nucleic acid hybridization. The deduced amino acid sequence of this insert is 94% identical to that of rat S10; no similarity to immunoglobulin sequences could be discerned. The reactivity of the anti-light chain antibodies with the putative Xenopus S10 facilitated the purification of the protein, by high-pressure liquid chromatography, from the 40S subunit of Xenopus ribosomes. Amino-terminal sequence analysis established the identity of the ribosomal protein with the protein encoded by the cDNA insert. To explore the basis for this unexpected cross-reaction, an "antibody transfer" experiment was carried out. Antibodies to Xenopus light chains were adsorbed to Xenopus S10 on a nitrocellulose strip, which was incubated with another strip containing separated heavy and light chains from Xenopus IgM. Antibodies migrated from the strip carrying S10 to the light chains, but not the heavy chains, on the second strip. These results suggest that this unexpected cross-reaction is due to the sharing of one or more epitopes by Xenopus immunoglobulin light chains and the ribosomal protein, S10.

Amino Acid Sequence↗