Wednesday 29 April 2020

The Non-coding RNAs of Eucaryotes


Messenger RNA, tRNA and rRNA are not the only RNA species present in cells. There are several other non-coding (they do not code for protein) RNA in the cell- small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), heterogenous nuclear RNA (hnRNA), micro RNA (miRNA), small interfering RNA (siRNA), telomerase and signal recognition peptide (SRP). It is important to appreciate that noncoding RNA are also transcribed from DNA- but unlike mRNA, they are not translated into protein. That is to say, all genes do not lead to protein as the end product- for some, the end product is RNA.

Some of the noncoding RNA are produced from introns (as below), which might seem non-intuitive as the generally held view is that introns do not code for anything.

The eucaryotic pre-mRNA is capable of being alternatively spliced in to different mRNAs and can therefore produce different proteins from the same DNA code. This happens in the "spliceosome". Unusually, the splicing reaction is not catalysed by proteins, but by non-coding RNA, called small nuclear RNA (snRNA). A similar situation is seen during protein synthesis, where rRNA, which forms 2/3 of the ribosome-the other third is protein- catalyses the peptide bond formation required to lengthen the polypeptide chain. Such catalytic RNA, which act like enzymes, are called ribozymes. It's thought that they hark back to very early evolution, when RNA was the main catalyst for living cells rather than protein.

There are 5 types of snRNA- U1, U2, U4, U5 and U6. There is no U3 snRNA. These associate with proteins, and together, the complex is is called snRNP. Around 90% of multiexonic mRNA in humans is subject to alternative splicing. The most common form of alternative splicing in humans is exon-skipping, followed by intron retention.

Bacteria have a single RNA polymerase, and do not have alternative splicing. There are 3 RNA Polymerases in eucaryotes- I, II, and III. RNA Polymerase I codes for most rRNA- 18S, 28S, and 5.8S. RNA Polymerase II codes for all protein coding RNA- ie the messenger RNA. RNA Polymerase III codes for tRNA, and also 5S rRNA. The S in rRNA refers to the rate of sedimantation in an ultracentrifuge. The larger the S value, the larger the rRNA.

Messsenger RNA only form 3-5% of the total RNA in the cell. Fully 80% of cellular RNA is comprised of rRNA. Thus, human beings contain some 200 rRNA genes per haploid genome, which are together responsible for making 10 million copies of each type of rRNA (28S, 5.8S, 18S and 5S) to constitute 10 million ribosomes.

The 200 rRNA coding genes are present in just 5 chromosomes- 13, 14, 15, 21 and 22. In all 5 chromosomes, these genes are located right at the very tip (end) of the short arms. 28S, 18S and 5.8S rRNA are all made initially as part of a larger 45 S pre-rRNA before being spliced. 5S rRNA is made separately. All but 18S RNA contribute to form the large 60S rRNA subunit. The smaller 40S subunit is comprised of 18S rRNA.

Many Small nucleolar RNAs are encoded on the introns of other genes, mainly for ribosomal proteins. They are synthesised by RNA Polymerase II and processed from excised Intron sequences.

The nucleolus is the cellular site for manufacture and processing of all noncoding RNA, and additionally carries the genes for tRNA. The 5 pairs of chromosomes mentioned above each make a portion of the nucleolus, which then fuse together to form one large nucleolus.

Antibodies to RNA Polymerase III in Systemic Sclerosis are associated with a higher risk of cancer.


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