Question

What is the concept behind RNA interference? Explain in terms of how it works.

What kinds of things are transcribed in the human genome?

How are the number of chromosomes and genome size related?

Answer 1

1. RNA interference, also known as RNAi is the process by which gene expression is regulated at the post-transcriptional level by other RNA molecules such as microRNAs(miRNAs) or small interfering RNAs(siRNAs). These small RNA molecules bind to a 'seed region' on the 3' UTR of mRNA transcripts and direct enzyme complexes to degrade their target mRNA molecules.

Background: The process starts with a double-stranded RNA that is homologous in sequence to the silenced gene. Drosha is a type III RNase endonuclease that converts a primary-mRNA molecule into a precursor miRNA molecule that's approximately 70 nucleotides long. This Pre-miRNA molecule is actively exported to the cytoplasm by Exportin 5.

The precursor miRNA is loaded onto Dicer (RNase type III endonuclease) which cleaves it into a 20 nucleotide mature miRNA duplex. One strand is selected to be biologically active and the other one is degraded. The single strand is loaded onto an Argonaute protein and formation of an RNA induced silencing complex (RISC) takes place.

RISC works by two mechanisms. Either by deadenylation (removal of PolyA tail) through deadenylases thereby leading to mRNA degradation or blockade of translation at the initiation step or at the elongation step. RISC bound mRNA can be localized to sub-cytoplasmic compartments known as P-bodies, where they are reversibly stored or degraded.

2. The human genome can be broadly classified into coding and non-coding regions. The non-coding portion makes up for the majority of the genome. Exons encode for various types of proteins, the non-coding genome encodes for pseudogenes, repetitive DNA sequences, transfer RNAs, small regulatory RNAs such as miRNAs, siRNAs, etc.

3. There is no relation between the number of chromosomes and genome size in eukaryotes, this is known as the C-value paradox.