FOM 5.4.1 Flashcards
What are the three forms of RNA processing?
Capping, splicing, and polyadenylation
What two forms of RNA processing happen co-transcriptionally?
Capping and splicing
Tell me about capping. What is it? Where? What type of bond? What is important about this bond?
7-methyl Guanosine cap, 5’ end, 5’->5’ triphosphate bond, impenetrable to exonuclease activity
What are the four way that capping influences function of mRNA?
increase stability, export to cyto, req’d for tln, identification of mRNA as cellular (not viral)
Polyadenylation. PolyA signal sequence? Two steps? # of A added? What is not required?
AAUAAA signal, cleavage then polyadenylation, 150-200A, no DNA template required
What are the four way that polyadenylation influences function of mRNA?
export to cyto, stabilize mRNA
Do all genes have introns? Examples?
No, histone proteins don’t have introns. Distrophin holds record w/ 79 exons and enormous amounts of introns
What are the two ways that the complexity of hnRNA conversion to mRNA leads to diversity?
alt splicing and terminaiton/polyA
Baby M.S. has hypotonic posture, inactivity and poor sucking, elevated creatinine kinase, then at 4 mo cannot control head/respiration. What’s the diagnosis, doc?
Spinal muscular atrophy
What is spinal muscular atrophy (SMA)? What gene expression is altered?
Primarily motor neuron degenerative dz, SMN1 (survival of motor neuron 1)
What is SMN1 typically involved with?
snRNP (small nuclear ribonucleo-protein) assembly
Which exon is typically not expressed in SMN2 that is normally expressed in SMN1?
Exon 7 ( prolly out of the scope, but Miles needs humbled every now and again)
What is the role of snRNP in mRNA splicing?
Recognition of conserved nucleotide sequences and creation of splicing assembly
What are the 3 steps of lariat structure/splicing?
PIC
Which snRNPs find recognize exon/intron boundary and A at the “branch point” of lariat
U1: donor exon/intron boundary U2: A at the “branch point”
What are the components of the spliceosome:
U1, U2 (Sean’s favorite band), U4, U5, U6
What are the four examples of alternative exon usage?
Cassette (exon skip), mutually exclusive, internal acceptor, alternative promoter
What % of human genes are alternatively spliced?
>90%
What splice variants of what gene lead to increased prostate cancer risk?
KLF6, a tumor supressor gene
What type of effect does KLFP-SV1 have on KLF6?
dominant-negative, it binds DNA preventing KLF6 from binding & blocking txn
If a prostate cancer is found to have a higher potential to metastasize, what can be said about the ratio of KLF6-SV1 /KLF6
High ratio
Is different usage of alt splicing always an indication of something gone wrong?
No, alternative splicing of glucocorticoid receptor to (+)/(-)
In B(not)-thalassemia, no B-chain synthesis occurs. What is the mutation mechanism?
Mutation kills acceptor site of splicing, so a cryptic splice site (best alternative) is used
What are the three mutations that alter splicing location?
1) kill acceptor, use cryptic (no good protein) 2) new, strong acceptor (a little good) 3) new donor splice site (frameshit; decent amt of good)
What are the three general types of mutation mechanisms that lead to splice variants for specific genes?
1) SNP alters splice donor/acceptor (B-thal) 2) SNP alters binding factor that regulates splicing (prostate CA) 3) SNP alters splicing machinery (SMA)
What are core elements?
demarcate where splicing occurs and are bound by snRNPs and other general factors that influence splice site utilization
What are Auxiliary splicing reg elements?
lie within introns or exons and bind proteins that promote or repress the choice of splice site, these are analogous to transcriptional enhancers/silencers
