Post-transcriptional regulation

[1][2] It also plays a big role in cell physiology, being implicated in pathologies such as cancer and neurodegenerative diseases.

[3] After being produced, the stability and distribution of the different transcripts is regulated (post-transcriptional regulation) by means of RNA binding protein (RBP) that control the various steps and rates controlling events such as alternative splicing, nuclear degradation (exosome), processing, nuclear export (three alternative pathways), sequestration in P-bodies for storage or degradation and ultimately translation.

In short, the dsRNA sequences, which will be broken down into siRNA inside of the organism, will match up with the RNA to inhibit the gene expression in the cell.

Modulating the capping, splicing, addition of a Poly(A) tail, the sequence-specific nuclear export rates and in several contexts sequestration of the RNA transcript occurs in eukaryotes but not in prokaryotes.

[1] In order for gene expression to proceed, regulatory proteins must bind to the RNA chain and remove the attenuation, which is costly for the cell.

[6] The stem-loop is followed by a run of U's (poly U tail) which stalls the polymerase, so the RNA hairpin have enough time to form.

[13] These complexes are essential for the regulation of gene expression to ensure that all the steps are performed correctly throughout the whole process.

Moreover, they affect mRNA stability by regulating its conformation due to the environment, stress or extracellular signals.

[3] Thankfully, due to new methodological advances, the identification of RBPs is slowly expanding, which demonstrates that they are contained in broad families of proteins.

[7] Overexpression can change the mRNA target rate, binding to low-affinity RNA sites and causing deleterious results on cellular fitness.

This area of study has recently gained more importance due to the increasing evidence that post-transcriptional regulation plays a larger role than previously expected.

Even though protein with DNA binding domains are more abundant than protein with RNA binding domains, a recent study by Cheadle et al. (2005) showed that during T-cell activation 55% of significant changes at the steady-state level had no corresponding changes at the transcriptional level, meaning they were a result of stability regulation alone.

[28] In another example, a mutated constitutively (persistently) expressed version of the oncogene c-Myc is found in many cancers.

These microRNAs normally repress expression of two genes essential for MMEJ, Lig3 and Parp1, thereby inhibiting this inaccurate, mutagenic DNA repair pathway.

This generates genomic instability through increased inaccurate MMEJ DNA repair, and likely contributes to progression to leukemia.

A prokaryotic example: Salmonella enterica (a pathogenic γ-proteobacterium) can express two alternative porins depending on the external environment (gut or murky water), this system involves EnvZ (osomotic sensor) which activates OmpR (transcription factor) which can bind to a high affinity promoter even at low concentrations and the low affinity promoter only at high concentrations (by definition): when the concentration of this transcription factor is high it activates OmpC and micF and inhibits OmpF, OmpF is further inhibited post-transcriptionally by micF RNA which binds to the OmpF transcript [ 18 ]