Flashcards in Lecture 20 Deck (19)
What is a non-coding RNA (ncRNA)?
A non-coding RNA (ncRNA) is a functional RNA molecule that is not translated into a protein
What are examples of structural ncRNA?
1) small nucleolar RNA (snoRNA) - modification and maturation of rRNA
2) small nuclear RNA (snRNA) - spliceosome assembly and function
What are examples of regulators of gene expression ncRNA?
1) Large ncRNA - regulate transcription of mRNAs from protein coding genes
2) microRNA - regulate translation of mRNAs from protein coding genes
What recognizes splicing sites?
Family of U1 proteins involving ribonucleoprotein (RNP) complexes with small noncoding RNAs. U1 attached to 1 exon while U2 attached to other exon. Proteins U3-6 assist in splicing
What is a summary of what snoRNA does?
1) Required for assembly and function of the snoRNP (ribonucleoprotein) complex
2) Active in the nucleolus for rRNA modification (pseudouridine and 2'-O-methyl ribose)
3) Proteins in the RNP complex catalyse these reactions at hundreds of nucleotides in each rRNA molecule
What is a summary of what microRNA does?
Micro RNAs (miRNAs) have a very small antisense RNA processed from a larger double stranded RNA precursor, complementary to 3' untranslated region of protein coding mRNAs, inhibiting their translation. More miRNA expression causes less mRNA translation
What is a summary of what long ncRNA does?
Long ncRNAs associate with promoter/enhancer regions of protein coding genes, interfering with their transcription
What does XIST (X inactivation specific transcript) RNA do?
It is a type of long noncoding RNA that is found as a single copy gene on the X chromosome. It mediates the gene dosage compensation process of X inactivation in females
What does IC (imprinting center) RNA do?
It is a type of long noncoding RNA that is found as single copy genes whose expression regulates transcription of mRNA gene clusters by genomic imprinting
What are rules to X chromosome inactivation in females?
Both X chromosomes are active in very early embryogensis but as development ensues, each cell in the female embryo inactivates one X chromosome, so
1) Inactivation is embryonic
2) Inactivation is random
3) Inactivation is perpetual
How does X inactivation occur?
1) X Inactivation Specific Transcript (XIST) gene encodes a 17kb noncoding RNA
2) Autosomal genes produce autosomal blocking protein to turn off transcription of one XIST gene on the future active X chromosome
3) XIST RNA inactivates an X chromosome, causing hypermethylation (of CpG islands) and transcriptional silencing of the genes on that X chromosome; XIST RNA production eventually ceases, however hypermethylation maintains X chromosome silence
What are characteristics of individuals with Prader-Willi syndrome?
Prader-Willi syndrome is a congenital (present from birth) disease. It affects many parts of the body. People with this condition are obese, have reduced muscle tone and mental ability, and have sex glands that produce little or no hormones
What are characteristics of individuals with Angelman syndrome?
Angelman syndrome (AS) is a neuro-genetic disorder characterized by severe intellectual and developmental disability, sleep disturbance, seizures, jerky movements (especially hand-flapping), frequent laughter or smiling, and usually a happy demeanor.
What is genomic imprinting?
Genomic imprinting is an epigenetic phenomenon by which certain genes can be expressed in a parent-of-origin-specific manner. It may also ensure transposable elements remain epigenetically silenced throughout gametogenic reprogramming to maintain genome integrity. It is an inheritance process independent of the classical Mendelian inheritance
Prader Willi Syndrome is ______ imprinted, while Angelman Syndrome is _______ imprinted.
Maternally (deletion in the dad, mom has mutant); Paternally (deletion in the mom, dad has mutant)
What is the imprinting center (IC)?
1) Controls transcription of groups of genes oppositely imprinted in male and female meiosis
2) Can produce two large non-coding RNAs: one produced only in female meiosis that directs hypermethylation (transcriptional silencing) of the PWS gene(s) and the other only in male meiosis that causes hypermethylation of the AS gene
What causes Prader-Willi and Angelman Syndrome?
70% of Prader-Willi and Angelman Syndrome caused by the large 15q11-13 deletion
23% of Angelman Syndrome cases caused by point mutations in the UBE3A gene
0% of Prader-Willi cases caused by point mutation: Prader-Willi is a contiguous gene syndrome (more than one gene
What is Uniparental disomy (UPD)
UPD occurs when two normal chromosomes from one parent show up in a daughter cell and none from the other parent are available. This usually arises as a second spontaneous event after an initial trisomy.
1) UPD15 from Dad: Angelman Syndrome
2) UPD15 from Mom: Prader-Willi syndrome