Biomedical subjects
Publications and source records attributed to Harsh H Kavi.
In Drosophila, the RNA interference (RNAi) genes participate in Polycomb (Pc)-mediated transgene silencing. Recently, the involvement of the RNAi genes in Pc silencing, pairing-sensitive silencing and long-range contacts among Pc-associated sequences has been explored. These Pc-associated sequences are involved with the control of the proper expression of developmental HOX genes.
The sex chromosomes of many species differ in dosage but the total gene expression output is similar, a phenomenon referred to as dosage compensation. Previously, diverse mechanisms were postulated to account for compensation in distantly related taxa. However, two recent papers present evidence that dosage compensation in Drosophila, mammals and nematodes share the property that there is an approximately two-fold upregulation of the single active X chromosome in each case.(1,2) The results suggest that a common mechanism might operate in these different cases.
Knowledge of the role of RNA in affecting gene expression has expanded in the past several years. Small RNAs serve as homology guides to target messenger RNAs for destruction at the post-transcriptional level in the experimental technique known as RNA interference and in the silencing of some transgenes. These small RNAs are also involved in sequence-specific targeting of chromatin modifications for transcriptional silencing of transgenes, transposable elements, heterochromatin and some cases of Polycomb-mediated gene silencing. RNA silencing processes in Drosophila are described.
The RNAi machinery is not only involved with post-transcriptional degradation of messenger RNAs, but also used for targeting of chromatin changes associated with transcriptional silencing. Two recent papers determine the global patterns of gene expression and chromatin modifications produced by the RNAi machinery in fission yeast.(9, 10) The major sites include the outer centromere repeats, the mating-type locus and subtelomeric regions. By comparison, studies of Arabidopsis heterochromatin also implicate transposons as a major target for silencing. Analyses of siRNA libraries from Drosophila, nematodes and Arabidopsis indicate that major repeats at centromeres, telomeres and transposable elements are likely targets of RNAi. Also, intergenic regions are implicated as targets in Arabidopsis.
Mutation of the multi-KH domain protein DPP1, which has single-stranded nucleic acid binding activity, suppresses heterochromatin-mediated silencing in Drosophila; it also disrupts the modification of histone H3 at lysine 9, and association of heterochromatin protein 1 on the heterochromatic regions, suggesting a role for DDP1 in heterochromatin formation.