Lecture 27 Flashcards
describe genomic imprinting and how it can lead to a disease state
genomic imprinting is caused by DNA methylation
basically, the methylated DNA of one parent is “shut down” so the other parent’s genes will be the only gene expressed in the offspring
Prader Willi Syndrome (PWS) is caused by a paternal deletion on chromosome 15 being expressed due to methylated maternal genes (if the maternal genes weren’t methylated, the maternal genes could have been expressed and the PWS avoided)
Females are _____ of the paternal and maternal X genes
mosiacs
Describe the decision of specialization method of controlling gene expressions
the specialization of cells occurs as the induction of or decisions NOT to induct different regulatory proteins are made
different specializations of cells are created with different combinations of collections of inducted proteins
Describe the coordinated gene expression method of controlling gene expressions
gene expression is triggered in response to need
ex. is glucocorticoid cortisol being heavily expressed in the morning and not being expressed at night
explain the difference between an unfolded protein that is ubiquitinated once and an unfolded protein that is ubiquitinated 10 times.
the protein that has a 10 ubiquitin chain will most likely be recognized, and therefore degraded by the proteasome before the protein with only one ubiquitin on it
the more ubiquitin, the more likely the protein is to be degraded
Describe the symptoms of Prader-Willi Syndrome (PWS)
Stage one: infantile hypotonia (floppy) and poor suck/feeding difficulties
Stage two: hyperphagia (uncontrollable eating) leading to early childhood obesity
hypogonadism
short stature
mental deficiency
describe proteasomes function and how that relates to their structure as well
a molecular machine that carries out the degradation of proteins that have been ubiquitinated
it is a hollow cylindrical structure with a cap on each end and a hollow chamber in the center
the cap binds to the ubiquitinated protein and acts as a gate
the chamber has 6 active sites that degrade proteins in an ATP dependent manner
An miRNA variant of SLITRK1 gene is associated with _____ _____ . SLITRK1 gene expression is decreased when miR-189 binds more efficiently to the same target sequence.
Tourettes Syndrome
this miRNA variant basically competes with the SLITRK1 gene for the same target sequence
Describe the decision of specialization method of controlling gene expressions
the specialization of cells from stem cells to their specific specialization is triggered by the expression of various genes
Describe the DNA methylation method of controlling gene expressions. be sure to mention the role of maintenance methyltransferase” and an example of a phenomenon caused by DNA methylations
methylated DNA sequences are silenced
methylation of cytosine occurs at “CG” sequences and is conducted/conserved through DNA replication cycles by maintenance methyltransferase
genomic imprinting is a phenomenon caused by DNA methylation
Explain how gene expression is regulated at the post-transcriptional level in terms of RNA.
Alternative splicing: can produce different forms of proteins from the same gene
Spatial localization of mRNA: there are several ways that mRNA’s leave the nucleus
Regulation via RNA stability: the 5’ cap and Poly A tail determine how long an mRNA structure will survive until it is degraded
What is IRP? state the name of the IRP involved in iron metabolism
Iron responsive regulatory protein: basically regulates what mRNA is translated and what mRNA isnt translated
cytosolic aconitase
What is IRE?
iron responsive elements: are recognition sites on mRNA for binding to a regulatory protein
describe the activation of the target protein degradation signal
phosphorylation of the signal via protein kinase
unmasking by protein dissociation
creation of destabilizing N-terminus
Describe the symptoms of Prader-Willi Syndrome (PWS)
Stage one: infantile hypotonia (floppy) and poor suck/feeding difficulties
Stage two: hyperphagia (uncontrollable eating) leading to early childhood obesity
hypogonadism
short stature
mental deficiency
describe what the serum levels of miR-141 and miR-29 can serve as biomarkers for, and how each of them presents
miR-141 is elevated in prostate cancer
miR-29 is decreased in heart disease
Explain how proteins are regulated by post-translational processing. Be sure to list the 3 types of post-translational modification that may occur in order to achieve a functional protein
post-translational processing is required in order for proteins to be functional and includes the following
folding/cofactor binding covalent modifications such as phosphorylation (via kinases) or acetylation binding to other subunits
Describe the steps and enzymes (E1, E2, E3) involved in the ubiquitination of unfolded or abnormal proteins
E1 is the ubiquitin activating enzyme that is involved in the first step by using it’s cysteine side chain to link to ubiquitin
E2 and E3 (or ubiquitin ligase) are complexed, and receive the ubiquitin from E1. E1 leaves
the target protein, which must have a degradation signal, is then bound to the complex by interacting with E3 (ubiquitin ligase)
each successive round of ubiquitination must begin with another E1 enzyme that brings the ubiquitin to the complex and adds it to the chain
The following are all examples of what?
Coordinated gene expression
Decision of specialization
DNA methylation
X chromosome inactivation
methods of controlling gene expression
Describe the RNA control of ferritin mRNA and transferrin receptor mRNA under condition of iron starvation
IRP binds to IRE of ferritin mRNA at the 5’ end which causes a decrease in ferritin mRNA, as cells do not need to store iron at this time
IRP binds to IRE of transferrin receptor mRNA at the 3’ end which causes an increase in TfR(transferrin receptor) mRNA so that more iron can be transported into the cell
True or False: Micro RNA’s bind to mRNA’s to activate the mRNA’s to produce large amounts of protein. explain why
False
microRNAs are regulatory RNAs that silence the expression of specific mRNA targets by binding to the 3’ UT end of the mRNA
this leads to either the degradation of the mRNA or just blocks the translation of that mRNA
describe the process by which microRNAs are synthesized and their path to silence mRNAs (probably not a huge deal)
made in the nucleus as precursor miRNA (with a hairpin loop) and are then “cropped” into maturity
this enters the cytoplasm where “dicing” occurs via a dicer enzyme
the microRNA joins with argonaute and other proteins to form “RISC” (RNA-induced silencing complex)
this RISC complex base pairs with mRNA, cleaves the RNA, and is then released as the mRNA fully degrades
Describe the X chromosome inactivation method of controlling gene expressions
occurs in females in order to prevent complications caused by an extra chromosome
one of the X chromosomes, randomly chosen, is inactivated by becoming highly condensed
list and describe variations in the regulation of gene expression
Genomic imprinting: differential expression of genetic material depending on the parent of origin
Epigenetics: regulation of expression of gene activity without altering the gene structure
X chromosome inactivation: one of the X chromosomes in a female will randomly be inactivated (turned to heterochromatin)
