Ch5 post-transcriptional regulation

• Posttranscriptional regulation of eukaryotic gene expression involves mRNA degradation, protein degradation, and protein synthesis.
• Prokaryotes (P) have different mechanisms of mRNA degradation and protein degradation compared to Eukaryotes (E).
• Posttranscriptional controls in prokaryotes include possible start transcription, possible attenuation, capping, splicing +3’ end cleavage, possible RNA editing, and nuclear export.
• Posttranscriptional controls in eukaryotes include possible start transcription, possible translational recoding, possible RNA (de)stabilization, retention and degradation, mRNA processing, and protein synthesis.
• Transcription to be initiated, the polymerase must first gain access to the promoter region at the beginning of a gene.
• If a protein has multiple domains, but the cell only needs one, it would be a lot of energy to transcribe all the domains via alternative splicing.
• Splicing events retain noncatalytic domains while ablating the catalytic domain to create C Ns with diverse functions.
• Each synthetase is converted into several new signaling proteins with biological activities “orthogonal” to that of the catalytic parent.
• Splice variants with nonenzymatic functions may be more general, as evidenced by recent findings of other catalytically inactive splice-variant enzymes.
• Promoter access is impaired by chromatin, which can inhibit transcription and must be removed or shifted for transcription to occur.
• Active promoters are found in nucleosome-depleted regions, which are flanked by specialized +1 and −1 nucleosomes on the downstream and upstream side of these regions, respectively.
• Chromatin opening is regulated differently for distinct classes of promoters.
• Translational regulation in the cytosol involves 5’ mRNA, 7 G (A) n, 3’ ORF, uORF, eIF, modification, sequestration, masking, blocking, cap-independent initiation, re-initiation, frameshifting, readthrough, recoding, breakdown, localization, cytoplasmic polyadenylation, mature mRNA, RNA interference.
• Translational recoding includes frameshifting, +1 frameshifting, nonsense suppression, stop codon recoding, and others.
• Posttranscriptional regulation in the nucleus involves elongation pause/termination, TATA box, alternative splicing, nuclear export, transcript cleavage, and others.
• In the case of Pol II, one class of human promoters contains CpG islands that can impair the assembly of inhibitory nucleosomes and facilitate polymerase access.
• Translational regulation in Eukaryotes involves general regulation of translation initiation, regulation after transcription initiation, and sequence-specific translational regulation.
• Nuclear poly(A) tail acquisition is a default process, but the position at which the mRNA 3' UTR is cleaved and polyadenylated is highly regulated for a large proportion of the genome, thereby determining the regulatory signals that will be present in the mature transcripts at their 3' UTRs.
• Silent mRNPs accumulate and in many cases are localized to specific parts of the cell, to then be reactivated by cytoplasmic poly(A) tail elongation at the precise time and specific place where their encoded proteins are needed.
• Translational repression and derepression are key elements in mRNA translation.
• mRNA degradation can be regulated by sequence-specific translational inhibition.
• Small RNA-mRNA interactions are a crucial aspect of mRNA regulation.
• These regulatory elements, in turn, will mediate mRNA deadenylation while stabilizing the translationally silent transcripts.
• Sequence-specific translational regulation is a crucial aspect of mRNA translation.
• Localization element and localization factor are key elements in mRNA localization.
• Competition between localization factor and local translation factor determines the localization of mRNA.
• Promoters such as these are often found at housekeeping genes that encode for proteins that are required in all the cell types of an organism.
• The activity of promoters that contain CpG islands can be altered by DNA methylation.
• Most somatic sexual characters are differentially determined by the 16 two dsx proteins, which act as transcription factors that sex-specifically enhance or repress a number of downstream male- and female-specific genes, implementing the two different routes of sexual differentiation.
• In females, the presence of TRA protein, together with the cofactor TRA2, initiates an alternative splicing pattern, which includes and terminates with exon 4, producing the female-specific DSXF isoform.
• Male Sxl transcripts produced from the late Pm promoter retain exon 3, resulting in premature termination of translation and absence of functional SXL protein.
• In males, the absence of TRA protein results in the default splice of dsx transcripts and the loss of exon 4, producing the male-specific DSXM isoform.
• In females, SXL protein blocks the canonical splice site and forces use of a cryptic splice site just downstream of the stop codons, creating an open reading frame which allows the production of active TRA protein.
• Tra codes for another RNA-binding protein that causes alternative splicing of doublesex (dsx), the next downstream element in the pathway.
• In males, the absence of SXL results in mRNAs that retain the stop codons in exon 2, leading to premature termination of translation and absence of any functional TRA protein.
• Like Sxl, tra produces transcripts that contain several stop codons at the beginning of exon 2.
• Sxl codes for an RNA-binding protein that regulates production of not only its own transcripts but also those of transformer (tra), the next gene in the sex-determination pathway.
• Only a fraction of Pol II promoters is active in a particular cell.
• These promoters are activated by transcription factors that are available in the nucleus.
• Transcription factors bind, in a sequence-specific manner, to DNA elements and can guide polymerases to their target promoters.