Biology of non-coding RNAs in cancer Flashcards
Mir-17-92 controls the expression of :
a) PTEN
b) TP53
c) Ras
d) BRCA1
e) Rb1
a) PTEN
MicroRNA profiling is informative of:
a) Tumor origin
b) Tumor type and sub-type
c) Mutations that can be targeted by targeted therapy
d) a and b are correct
e) All of the above
d) a and b are correct
P-bodies are:
a) sites in the cytoplasm where pre-miRNA are processed by Drosha
b) potential targets for miRNA-mediated anti-cancer therapy
c) proteins that bind mature, single-stranded siRNAs and miRNAs
d) sites in the cytoplasm where there is high activity of enzymes dedicated to mRNA turnover
e) none of the above
d) sites in the cytoplasm where there is high activity of enzymes dedicated to mRNA turnover
Who were the researchers involced in studying C-Elegans development, and discovering the lin4 gene
Rosalin Lee and Victor Ambros
What change did Rosalind Lee and Victor Ambros observe in C.Elegrans development that affected all cells
They observed that a change in one cell resulted in the same change in all cells
What was the focus of the search for mutations by Lee and Ambros, and what gene did they identify
They were looking for mutations influencing the lin-14 gene and identified the lin-4 gene, which encodes small RNA
What was the relationship between the variants of lin-4 namely lin-4S and lin-4L
They postulated that lin-4S was derived from lin-4L due to size differences
How did lin-4 interact with lin-14 and what was its effect on lin-14
Lin-4 was found to bind to seven sites in the 3’UTR of lin-14 suppresing its expression
What significant discovery was made eight years after identifying lin-4 and lin-14’s interaction
The discovery of let-7 miRNA in C.Elegans, which showed homology in drosophila and humans, indicating conservation acroess species
What was the observed consequence of let-7 mitations in C.elegans and what resemblance did it show?
C-elegans let-7 mutants exhibited continuous cell division and failure to differentiate, resembling traits seen in cancer
How did let-7 miRNA control the expression of RAS gene in both C elegans and human cells
Let-7 could bind multiple times to the homolog of Ras in C.elegans and human cells, effectively shutting down Ras expression, which is a proto-oncogene
Where are human miRNA genes frequently located and what is their association with cancer
Human miRNA genes are often found at fragile sites and in genomic regions associated with cancers
What is the significance of the miR-17-92 amplicon in relation to lymphoma
It represents a piece of the genome that is amplified in lymphomas, particularly at the 13q31locus, and collaborates with c-Myc, accelerating lymphoma progression, as seen in Burkitt’s lymphoma
What is the source of miRNAs in the genome and which enzyme transcribes them
miRNAs are transcribed from the genome by RNA pol II
What is the initial transcript of miRNAs and what is its name
The primary transcript is knows as pri-miRNA
Where does the processing of miRNA occur, and what enzyme is involved in this step
processing occurs in the nucleus by the microprocessor complex, which cleaves the hairpin structure of pri-miRNA to form pre-miRNA, which is then transported to the cytoplasm
What role does Dicer play in miRNA biogenesis
Dicer enzyme chews a loop in pre-miRNA, releasing a 21-nucleotide complex
After Dicer processing, where does the complex from pre-miRNA go, and what happens?
the complex is loaded onto the RNA-induced silencing complex (RISC) where the Argonaute protein binds the small RNA and cleaves one of the two strands via slicing
What challenges were faced in determining the structure of Human Argonaute 2, and what does its structure compromise
It was challenging du to crystallization difficulties. The structure includes 2 lobes : one with PIWI and MID domains folded together and the other PAZ+N domains.
What specific function does the PIWI domain of Argonaute proteins serve in miRNA functionality
PIWI domains functions as a RNAse domain and carries out the slicing activity by cleaving target RNAs
Why do the majority of mRNA targets not fully base-pair with miRNAs and can you provide an example
its intentional, for instance the middle genes of the lin-14 mRna did not fully base-pair with the lin-4 microRNA
How do miRNAs impact gene expression and what are the mechanisms through which they act
miRNAs can repress tranlsation, recreuit CCR4-NOT to degrade mRNA, and destabilize mRNA leading to its decay
What is the different mechanisms through which miRNA mediates gene silencing
miRNA, along with co-factors like GW182, can repress translation. It can also recruit CCR4-NOT, which deadenylates the mRNA’s 3’end (poly A tail) and it can induce mRNA decapping leading to destabilization and decay
What are P bodies, and why are they suspected as a site for miRNA function
P bodies are regions within the cytoplasm of eukaryotic cells containing enzymes involved in mRNA turnover. They are suspected sites for miRNA function because miRNA-targeted mRNAs are recruited to P bodies, where they can be destabilized or sequestered from the translational machinery
