Both are initiated through degradation of the mRNA's poly(A) tail, resulting in removal of the mRNA's 5' cap. 5'-to-3' degradation of the transcript occurs by XRN1 exonuclease in cytoplasmic bodies called P-bodies. 3'-to-5' degradation of the transcript is conducted by the exosome and Ski complex. Translational repression RISC can modulate the loading of ribosome and accessory factors in translation to repress expression of the bound mRNA transcript. Translational repression only requires a partial sequence match between the guide strand and target mRNA. Translation can be regulated at the initiation step by: preventing the binding of the eukaryotic translation initiation factor (eIF) to the 5' cap. It has been noted RISC can deadenylate the 3' poly(A) tail which might contribute to repression via the 5' cap. preventing the binding of the 60S ribosomal subunit binding to the mRNA can repress translation. Translation can be regulated at post-initiation steps by: peptide degradation, promoting premature termination of translation ribosomes, or, slowing elongation. There is still speculation on whether translational repression via initiation and post-initiation is mutually exclusive. Heterochromatin formation Some RISCs are able to directly target the genome by recruiting histone methyltransferases to form heterochromatin at the gene locus, silencing the gene. These RISCs take the form of a RNA-induced transcriptional silencing complex (RITS). The best studied example is with the yeast RITS. RITS has been shown to direct heterochromatin formation at centromeres through recognition of centromeric repeats. Through base-pairing of siRNA (guide strand) to target chromatin sequences, histone-modifying enzymes can be recruited. The mechanism is not well understood; however, RITS degrade nascent mRNA transcripts. It has been suggested this mechanism acts as a 'self-reinforcing feedback loop' as the degraded nascent transcripts are used by RNA-dependent RNA polymerase (RdRp) to generate more siRNAs. In Schizosaccharomyces pombe and Arabidopsis, the processing of dsRNA targets into siRNA by Dicer RNases can initiate a gene silencing pathway by heterochromatin formation. An Argonaute protein known as AGO4 interacts with the small RNAs that define heterochromatic sequences. A histone methyl transferase (HMT), H3K9, methylates histone H3 and recruits chromodomain proteins to the methylation sites. DNA methylation maintains the silencing of genes as the heterochromatin sequences can be established or spread. DNA elimination The siRNA generated by RISCs seem to have a role in degrading DNA during somatic macronucleus development in protozoa Tetrahymena. It is similar to the epigenetic control of heterochromatin formation and is implied as a defense