siRNA - Small Interfering RNAs

Small interfering RNAs, or siRNAs, are non-coding RNAs, about 22 nucleotides long, that regulate mRNA synthesis and stability.

siRNA can originate from within the cell by DNA transcription, can be processed from viral RNA, or can be added by scientists for experimental purposes.

siRNAs are processed from long double-stranded RNA. This RNA is cleaved into multiple short siRNAs with the help of an endonuclease, Dicer. 

Each siRNA then binds to Argonaute, along with other proteins, leading to the formation of the RNA induced silencing complex, or RISC.

In RISC, the RNA guide strand is separated from its complementary strand and remains in the complex, so it can then pair with the target mRNA. Then, the target mRNA is cleaved with the help of Argonaute and subsequently degraded in the cytoplasm. 

During their life cycle, RNA based viruses enter a host cell and produce double-stranded RNA. This RNA is recognized by Dicer and processed into siRNA. These siRNAs help fight viral infections by promoting the degradation of viral mRNA. 

In the nucleus, centromere-associated DNA repeats encode transcripts that are processed by Dicer to produce specific types of siRNA.  Unlike cytoplasmic siRNA, they inhibit mRNA synthesis and promote heterochromatin formation, which can regulate transcription.

These siRNAs bind to multiple proteins, including Argonaute, to form the RNA-induced transcriptional silencing, or RITS, complex.

The siRNA directs RITS to an active transcription site, where it binds with nascent mRNA. This binding then leads to the recruitment of additional proteins that modify nearby histone proteins and promote heterochromatin formation. 

This makes specific genes inaccessible, inhibiting transcription initiation in the target region and silencing transposons.