POST TRANSCRIPTIONAL MODIFICATION

LEARNING OBJECTIVE

Define post transcriptional modification

Define introns and exons
Describe the structure of primary transcript
Define the post transcriptional modifications of the primary transcript with their
significance
Discuss the clinical significance of the abnormal post-transcriptional modifications

POST TRANSCRIPTIONAL MODIFICATION OF RNA

A primary transcript is a linear copy of a trnscriptional unit, the segment of DNA

between specific initiation and termination sequences.
The primary transcripts of both prokaryotic and eukaryotic tRNAs and rRNA are post
transcriptionally modified by cleavage of the original transcripts by ribonucleases.
tRNAs are then further modified to help give each species its unique identity.
In contrast, prokaryotic mRNA is generally identical to its primary transcript, whereas
eukaryotic mRNA is extensively modified post transcriptionally.

RNA
Transcriptional Modification

Ribosomal RNA
Ribosomal RNAs of both prokaryotic and eukaryotic cells are synthesized from long precursor
molecules called preribosomal (45S)RNAs. The 23S, 16S and 5S ribosomal RNAs of prokaryotes
are produced from a single RNA precursor molecule, as are the 28S, 18S, and 5.8S rRNAs of
eukaryotes.

rRNA
Eukaryotic 5S rRNA is synthesized by RNA polymerase III and is modified separtely. These
precursors are cleaved to yield intermediate-sized pieces of rRNA, which are further trimmed
to produce the required ribosomal RNA species. (Note: some of the proteins destined to
become components of the ribosome associate with the rRNA precursor prior to and during its
post-transcriptional modification in the nucleolus.)

Transfer RNA
Both eukaryotic and prokaryotic transfer RNAs are also made from longer precursor molecules
that must be trimmed. Other post-transcriptional modifications include additin of a CCA
sequence by nucleotidyltransferase on the 3 terminal end of tRNAs, and modification of bases
at specific positions to produce unusual bases

tRNA

Eukaryotic messenger RNA

The RNA molecule synthesized by RNA polymerase II (the primary transcript, sometimes called
hnRNA for heterogeneous nuclear RNA) contains the sequences that are found in cytosolic
mRNA. This primary transcript is extensively modified after transcription.
These modification may include.

1. 5 Capping This process is the first of the processing reactions for hnRNA. The cap is a 7methyl-guanosine attached backward through a triphosphate linkage to the 5 terminal end of
the mRNA. The addition of the guanosine triphosphate part of the cap is catalyzed by the
nuclear enzyme guanylyltransferase. Methylatin of this terminal guanine occurs in the cytosol,
and is catalyzed by guanine 7 methyl-transferase. S-adenosylmethionine is the source of the
methyl group.

mRNA

mRNA
Additional methylation steps may occur. The addition of the 7-methylguanosine cap
through the unusual 5 5 triphosphate linkage appears to facilitate the initiation of
translation and helps stabilize the mRNA. Eukaryotic mRNAs lacking the cap are not
translated efficiently

2. Addition of a poly-A tail: Most eukaryotic mRNAs (with several notable

exceptions, including those coding for the histones and some interferons) have a
chain of 40 to 200 adenine nucleotides attached to the 3 end.
This poly-A tail is not transcribed from the DNA, but rather is added after
transcription by the nuclear enzyme poly-A polymerase.
These tails may help stabilize the mRNAs and facilitate their exit from the nucleus.
After the mRNA enters the cytosol, the poly-A tail is gradually shortened.
(note: A consensus sequence, called the polyadenylation signal sequence, found
near the 3-end of the gene, signals that a poly-A tail is to be added to the mRNA)

Removal of introns

Maturation of eukaryotic mRNA may involve the removal of RNA sequences (introns, or
intervening sequences) that do not code for protein from the primary trartscript
The remaining coding sequences, the exons, are spliced together to form the mature
mRNA. (note : some eukaryotic primary transcripts contain no introns, others contain a
few introns, wherease some, such as the primary transcripts for the chains of
collagen, contain more than 50 intervening sequences that must be removed before the
mature mRNA is ready for translation)
small nuclear RNAs (snRNAs), in association with proteins forming small nuclear
ribonucleoprotein particles (snRNPs),
facilitate the splicing of some exon segments by forming base pairs with each end of the
intron.
This binding brings the sequences of the neighboring exons into the correct alignment
for splicing , resulting in the excision of the intron.

REFRENCE

Post transcriptional Modification

(lipponcott chapter 30)

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