5 How do splicing and the RNAi mechanism regulate which mRNA

5. How do splicing and the RNAi mechanism regulate which mRNA molecules are translated? Which small RNA molecules are required for each process?

Solution

The splicing and the RNAi mechanism (microRNA & small interfering RNA (siRNA)) regulate which mRNA molecules are translated as siRNA or snRNA is also known as U-RNA as it contains many uridine contents in its complex structure. This is composed of 150 nucleotides nearly to produce spliceosomes and to act along with snRNP. This snRNA has a predominant role in splicing.

The RNA-induced initiation of transcription silencing complex (RITC): Inside the nucleus, genomic DNA is going to identify initially by this complex using single stranded RNA or microRNAs associated with recruiting chromatin remodeling protein for the silencing initiation and transcription repression.

MicroRNA\'s (miRNA) are the small non-coding products of gene of 21 to 27 nucleotides length. These miRNAs cause gene silencing by the inactivation of mRNA and thus, regulates gene expression (post-transcriptional gene regulation by binding to 3\'- UTR region of target mRNA). Micro RNA\'s are known to attack genes by inhibiting the translation from taking place. One miRNA can silence many mRNAs because the 3\'-UTRs (untranslated regions) of mRNAs have some common seed sequences to which these miRNAs can bind and trigger gene silencing.

MiRNA and SiRNAs are regulatory RNA which can silence the mRNA either by cleavage or by base pairing to the mRNA thus “regulates transcription” & translation. Sometimes these RNAs can regulate post-transcritional activity of mRNA

Small interfering RNA (siRNA) and micro RNA have both can silence gene expression of other foreign genes

Small interfering RNA and micro RNA are double standard RNAs

Dicer: it is also referred as endoribonuclease Dicer. It has activity of cleaving double-stranded RNA and pre –microRNA into specific fragments of RNA 20 to 15 kb (double stranded). This enzyme is also known as helicase with RNase. This enzyme called dicer and large RNA molecules produces small interfering RNA and micro RNA.

Gene expression & dicer: The process of generation of messenger RNA from genome of DNA in the presence of RNA polymerase and transcription factors is known as “gene expression”. Dicer influences gene expression by binding to “nascent mRNA” to cut into small fragments result in negative feedback of gene expression

Diffrenece: siRNAs usually originates from mRNAs exerts perfect action on targets;

RITS binds with siRNA and causes RNA transcriptional silencing whereas RISC cleaves mRNA. SWR1 –switch remodeling causes chromatin remodeling allows RNAase to enable transcription with a variant H2AZ. Imitation switch complex
(ISWI) enable transcriptional silencing is by displacing nucleosome positions from open to close.

For example,

In fission yeast, defective RNA interference (RNAi) is leading to loss of H3K9 methylation at cetromere result in loss of centromere function. Through a series of transcriptive and Dicer related activities, siRNAs are formed that are required for recruiting RITS complex to the centromere and heterochromatin formation. RNA-dependent RNA polymerase II is mainly responsible for the generation of short- lived siRNA finally a double stranded dsRNA is generated from this siRNA by dicer. These siRNA are complexed with argonaute result in Ago1 blockade finally RITS (RNA-induced initiation of transcriptional silencing) is recruited for co-transcriptional and post-transcriptional silencing result in assembly of heterochromatin to the centromere