Protein Translation and Endosymbiotic Organelles - Exam 1

translation

process of decoding the nucleic acid message into the protein language

information is stored in triplet codons responding to individual AAs, 64 codons

start codon - AUG - methionine

reading frames

determines proper translation

triplet codons allow for 3

ribosomes

translation machines

small and large subunit - composed of RNA and proteins

tRNAs

transfer the message from teh nucleic acid codon to an AA

non-coding RNA - single stranded allowing for many different shapes/functions

structure - AA at one end, RNA anti-codon at the other end

synonymous (point) mutation

point mutation that results in no change in AA

silent mutation

non-synonymous mutation

effect depends on location on protein and which AA swap happens

single base pair deletion

leads to a frame shift which typically results in a premature stop codon

can be detrimental

ADAMTS17

secreted protease (molecular scissors)

proteases play important roles in development and maintenance of the ECM including fibers

dysfunctional ADAMTS17 protease results in a failure to maintain the fibers that hold the ocular lens in place

• autosomal recessive

• homozygous - loss of function

• heterozygous - attenuation of function (can have some intermediate phenotypes

• doesn’t appear until 3y+

benefit of introns

increase protein repertoire by alternative splicing

regulate gene expression (when and how much)

U1 snRNA - binds to splice sites nad recruits TFs close to promoter to increase transcription, increased exon length leads to less expression bc RNA polymerase and TFs too far to re-initiate

antibiotics and protein synthesis

many (clindamycin) inhibit protein synthesis in prokaryotic ribosomes

Eukaryotic ribosomes are insensitive

exception some protozoan parasites (toxoplasma, coccidia) have plastids with their own ribosomes which are prokaryotic in nature

ribosomes assembly

ribosomal proteins made in cytoplasm → nucleus via nuclear pores → nucleolus, assembled with RNA → cytoplasm

disruption of assembly → nucleolar stress → apoptosis

ribosomal haploinsufficiency

mutation in one allele of a ribosomal protein leading to half as much of that subunit, causes excess of other subunits

assembly disrupted → excess subunits activate p53 signaling → nucleolar stress → cell cycle arrest and/or apoptotic cell death

diamond blackfan anemia

human disease (has been described in dogs)

ribosomal haploinsufficiency → mutation in genes encoding ribosomal subunits → apoptosis in erythroid progenitors → production of RBCs impared → severe anemia

endpsymbiotic organelles

organelle genome, double membrane

mitochondria, plastids

mitochondrial genome

small - 17 thousand bp

rRNAa and tRNAs for translation

proteins for oxidative phosphorylation (~100)

~1,500 proteins in mitochondria, 13 proteins encoded on mtDNA, all others are nuclear encoded and imported

mitochondria functions

energetic roles - production of ATP by cellular respiration

metabolic synthesis roles - nucleotides, lipids, heme

signaling roles - apoptosis

PROCESSORS of the cell

mitochondrial disease

can be from nuclear or mitochondrial DNA

mtDNA genetic disorders are maternally inherited (mitochondria are inherited exclusively from the oocyte)

• cells contain many mitochondria

• heteroplasmy: variation in oocyte mutant mitochondrial load (loading is random)

sensory ataxic neuropathy in golden retrievers

only maternal inheritance

mild to moderate pathology (heteroplasmy) - wobbly gait, postural deficits, diminished spinal reflexes

caused by a mutation in mtDNA - single bp deletion in a tyrosine tRNA → defective tRNA impairs translation of mitochondrial genes