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what is stability?
the extent to which RNA molecules retain its structural integrity and resists degredation
how is RNA stability controlled?
through increases and decreases in stability
what are RNases?
nucleases that can degraade RNA, and are secreted to kill things outside of the cell
what is the purpose of controlling mRNA stability/duration?
controls the amount of proteins produced, or how many mRNA are produced from a single gene
how is mRNA able to undergo fast regulation?
it’s half time is much shorter than a regular cell cycle
when does mRNA become less stable?
if the mRNA is missing its cap or polyA tail
when is polymerase 2 transcription shut down?
immediately, when mRNA starts degrading
how does mRNA become more stable?
with higher translation speed, as it causes more dense ribosomes
how can degradation rate be accurately measured?
when synthesis is shut down
what is the degradosome made up of?
RNase, PNPase, enolase, helicase
why is very stable RNA bad?
it can cause human disease
what can increase stability in mRNA?
sequences that form secondary and tertiary RNA structures, 5’ cap, polyA tail, stabilizing elements, and RNA binding proteins
what is the degradosome?
major machinery that degrades mRNA in prokaryotes
what mRNA factors affect degradosome activity?
translation efficieny, secondary structures, secondary structures, or short polyA/oligoA tails
what is a RNP (ribonucleoproteins) particle?
the form mRNA takes in the cell - complex form with RNAs and proteins
what are RBPs?
RNA binding proteins
what is the purpose of RBPs?
catalogue tags - signal cellular processes and locatinos
how many tags does mRNA have?
several - different mRNAs have distinct but overlapping RBPs
what is a regulon?
set of mRNAs that share a specific type of RBP tag
what are the two steps in a mRNA degradation event?
recognizing and tagging mRNAs that need to be degraded, and recruitment of the degradation machinery by the tags
what is involved in the second step in a mRNA degradation event?
two machineries are involved; a 5’ to 3’ exonuclease Xrn1 that acts after decapping, and a 3’ to 5’ decay occurs by the exosome after deadenylation
what is the exosome?
a highly conserved complex involved in degradation in eukaryotes
which degradation is the major route, from Xrn1 or the exosome?
if each route is blocked, it’s determined that the 5’ to 3’ end is the major route from Xrn1
what is involved in the first step in a mRNA degradation event?
degredation systems will degrade mRNA that’s deemed as no longer needed or supposedd to be downregulated, through deadenylation independent or dependent pathways
what is deadenylation-dependent degradation?
occurs when a shortened polyA tail is tagged - responsible for the degradation of most mRNAS, and is triggered when the polyA tail reaches 10 nucleotides
what is deadenylation-independent degradation?
occurs when tagged by other mechanisms, which eventually recruit Xrn1 or exosome for degradation. 4 additional pathways are involved, including independent decapping, oligoU-dependent degradation of histone mRNAs, endonucleolytic cleavage, and miRNA mediated silencing
what is miRNA?
short RNA strand that was first discovered in C elegans, and regulates 50% of mRNA
what is RISC?
RNA-induced silencing complex - a protein complex made up of miRNA, which targest mRNAs that have complementary sequences with miRNA tags
what is the pathway of microRNA mediated silencing?
drosha and dicer cleae off different parts of pre-miRNA, and the strand separaes before becoming mature. proteins are then associated, and the miRNA runs around the cell lookoing for complementary sequences to degrade.
what is RNAi?
RNA interference - it can insert and sequence into pre-miRNA, which leads to it becoming selective to the mRNA inserted
is mRNA localized?
yes - it can localize to specific regions of the cell
what are the three purposes of subcellular localization?
localized translation in specific cell compartments, different inheritance of specific mRNAs, and the setting up of embryonic body plan