Control of Gene Expression - part 1

Attenutation = Premature termination of transcription. 

Tat-Tar gene regulation in HIV:

Normally, in host cell, transcription of HIV virus will be terminated by host cell to prevent trascription occur. To avoid this, HIV transcribes a Tat protein that binds to the stem loop Tar on RNA sequence of HIV,  allows for elongation of mRNA to be made.

Riboswitch :

It is a part of mRNA that can "sense" small molecules in which binding of these small molecules will affect the gene activity. Riboswitch often can be divided into 2 parts: one is aptamer which binds the small molecules that regulates gene expression, and the other is platform that responses upon the conformation change based on the interaction of small molecules with aptamers.





Alternative RNA splicing:

This is one form of control transcription based on alternative of splicing. There are 4 patterns of alternative RNA splicing: option exon, optional intron, mutually exclusive exons and internal splice site. Because of this mechanism, even with a small amount of genes in cell can express million different proteins based on the stimulation under some certain conditions. This alternative splicing can be controlled in many different ways. Many distinct ways to control and alternate RNA splicing includes the intron sequence ambiguity, regulated splicing ( involve both repressor and activator), change in the site of RNA trasnscript cleavage.

Intron sequence ambiguity: 

the standard spliceosome mechanism for removing intron sequences is unable to distinguish clearly between two or more alternative pairing of 5' and 3' splice site, so that different choices are made by chance on different transcripts that occurs on transcriptional level.

Regulated splicing:

Splicing is controlled by both repressor and activator at the trancriptional level.

A change in the site of RNA transcript cleavage:

While transcribing to synthesize new RNA, for somehow, the elongation can be controlled by RNA cleavage reaction that is catalyzed by additional factors and results different size of RNA strand and alternate the C-terminus of the resultant protein. During the 3' end cleavage for additional pol A tail, the factor CPSF will recognize the cleavage site, allowing for pol A tails to be added. However, in some certain circumstances, CPSF might recognize different cleavage site, and results different size of mature mRNA.

For example: B-cell switches from anchored Ab to secreted Ab. Note that anchored Ab has hydrophobic sequence at C-terminal that allows it to anchor into cell membrane while secreted Ab does not have hydrophobic sequence. Also, that anchored Ab has a longer sequence than secreted Ab due to the cleavage process.

RNA editing:

this mechanism alters the nucleotide sequences of RNA transcripts once the are synthesized and thereby changes the coded message. This process involves guide RNA ( that is complementary in sequence to one end of the region of the transcript to be edited) or deamination of nucleotides ( change from A to I or C to U).

If the edit occurs in a coding region, it can change the amino acid sequence of the protein or produce a truncated protein.

If edits occur outside the coding sequences, it can affect the pattern of pre-mRNA splicing, the transport of mRNA from the nucleus to cytosol, or efficiency of RNA  being translated.