Cotranscriptional Chromatin Remodeling by Small RNA Species: An HTLV-1 Perspective

Figure 2

Mechanisms of siRNA-induced transcriptional silencing. miRNA/siRNA is imported into the nucleus from the cytoplasm after processing by Dicer through the nuclear pore complex. Alternatively, Dicer can also localize in the nucleus, allowing siRNA generation and amplification within the nucleus itself. Change in gene expression at the chromatin level directed by siRNA through the RNA-induced initiation of transcriptional silencing complex can be the outcome of a number of interactive mechanisms. Firstly, protein components of the RITS complex possessing both chromatin and RNA binding properties enable siRNA/miRNA to directly bind DNA. siRNA have homologous regions to the dg and dh regions of centromeric heterochromatin indicating a direct interaction between the two components. Secondly, miRNA can methylate promoter regions of genes or epigenetically cause the assembly of histone modifying proteins, changing the transcriptional state of chromatin. Thirdly, an interaction between siRNA and nascent mRNA transcribed from the centromeric region not only causes transcriptional repression of that region but also serves as an siRNA self-amplifying mechanism that uses degraded mRNA as a source of single-stranded RNA. Some of this ssRNA is amplified by RNA-directed RNA polymerase (RdRP) components which generate dsRNA further processed by nuclear Dicer into mature siRNA that augments silencing.