Epigenetics in Cancer 2 Flashcards
What is a transcriptome?
All the transcribed sequences in a genome
How common are non-coding RNA genes in the human genome?
Make up about 98% of the human genome, while the exact number of non-coding RNAs is unknown it is suspected there could be thousands
What are the two classes that non-coding RNAs can be broken into?
Small non-coding RNAs of under 200 bases and Long non-coding RNAs which are greater than 200 bases, there has been a proposed regulatory mechanism for both of these classes with each having a unique mechanism of action
What are the different classes of small non-coding RNAs?
Promoter associated RNAs
PIWI interacting RNAs, miRNAs,, snoRNAs, sdRNA, endo-siRNA
What are miRNAs?
Small non-coding RNA molecules found in plants and animals
These function by binding to complementary sequences on mRNA molecules, blocking translation or causing degradation allowing miRNAs to regulate gene expression
How are miRNAs produced?
miRNA genes are transcribed by RNA polymerase II to produce a pri-miRNA
Drosha and Digeorge syndrome critical region gene 8 mediate the initial processing step to convert the pri-miRNA to a pre-miRNA
The second processing step occurs through RNAse Dicer III which generates the miRNA/mRNA duplex
Dicer, TRBp or PACTR and argonaute 1-4 are responsible for pre-miRNA processing and RISC assembly
An unknown helicase is thought to mediate unwinding of the duplex while one strand remains the mature miRNA on ago
What is the miRNA mediated pathway in cancer?
Abberant miRNA expression levels can lead to either repression of tumour suppressor genes or derepression of tumour oncogenes
What are long non coding RNAs?
These are non coding RNAs which are over 200 bp long and can potentially reach over 100kb
They have a gene structure similar to a protein coding gene so they are capable of being spliced, capped, polyadenylated and edited
Exist in the nucleus, mitochondria and cytoplasm
Expression is cell type specific
How do long noncoding RNAs interact with other molecules?
Many, such as HOTAIR and XIST have protein binding domains required for their functions
They can also interact directly with DNA to form triplex structures or traditional duplex ones through base-pairing
Can also from base pair interactions with other RNA molecules to regulate miRNA targeting and splicing regulation
What is the cis-tether classification of long noncoding RNA function?
lncRNA tether to their site of transcription and regulate the expression of a nearby protein such as XIST
What is the trans regulation classification of long noncoding RNA function?
Long noncoding RNA can associate with DNA binding proteins and regulatory proteins to localize and affect the expression of the targets such as HOTAIR
What is the allosteric modification classification of long noncoding RNA function?
Long noncoding RNA can bind to regulatory proteins and change their activity as proposed for the CCND1
What is the decoy classification of long non-coding RNA function?
Long non-coding RNAs bind to protein complexes and prevent them from binding to their proper regulatory targets as proposed for GAS5
What is the role of noncoding RNAs in cancer progression?
Long and short ncRNA may act as tumour suppressor gene or oncogene
What is the function of long non-coding RNAs in the cytoplasm?
These regulate translation for example the UCHL1 mRNA is complemented by an antisense lncRNA, which in response to stress is shuttled to the cytoplasm where via an antisense complementary to the UCHL1 AUG initiation codon and combined inverted SINEB2 domains increases UCHL1 protein synthesis
