BMS100 Central Dogma Post-learning PDF

Central Dogma Post-learning Dr. Rhea Hurnik BMS100 Regulation of protein synthesis In class we looked at the basic of transcription and translation. However, a cell can regulate the amount of a particular protein available to a cell by regulating the: § 1. Amount of transcription that occurs § 2. Th...

Central Dogma Post-learning Dr. Rhea Hurnik BMS100 Regulation of protein synthesis In class we looked at the basic of transcription and translation. However, a cell can regulate the amount of a particular protein available to a cell by regulating the: § 1. Amount of transcription that occurs § 2. The stability of mRNA transcript § 3. The location of the protein § 3. Destruction of the protein Coming later 1. Transcription regulation Remember the nucleosome? § Structural unit for DNA packaging 1. Transcription regulation - histones Histones are highly dynamic structures regulated by a host of nuclear proteins. § Eg. 1 Chromatin remodeling complexes can reposition nucleosomes on DNA to either expose or obscure gene regulatory elements (eg. Promoters) § Eg. 2 Chromatin writer complexes can carry out histone modification such as methylation, acetylation, or phosphorylation. 1. Transcription regulation – histone modification Eg. 2 Histone modifications § Histone acetylation tends to open chromatin & increase transcription § Performed by histone acetyltransferases (aka HAT) Deacetylation reverses these changes and promote chromatin condensation 1. Transcription regulation – histone modification cont. Eg. 2 Histone modifications § Histones and DNA can both be methylated Histone methylation can promote transcriptional activation or repression (depends on the histone residue) DNA methylation typically results in transcriptional silencing 2. mRNA stability The longer an mRNA lasts in the cytosol, the more protein will be made via translation. § Remember that some of the non-coding forms of RNA (miRNA or siRNA) could promote the destruction of an mRNA transcript § Specific proteins can also bind to mRNA and prevent its degradation to results in more protein synthesis 2. mRNA stability Example: Transferrin § Protein receptor that brings iron into a cell Low cellular iron levels High cellular iron levels 3. Targeting to cellular location A cell can limit a protein to a particular cellular location § Proteins needed for intracellular cytosolic use are translated on free ribosomes in the cytosol § If destined for the nucleus, mitochondria, or peroxisomes: Once translated in the cytosol, a specific amino acid signal in the polypeptide will target the protein for its intracellular location 3. Targeting to cellular location Proteins destined for lysosomes, ER, cell membrane or secretion need to be directed to the rough ER (RER) for translation in a process called co-translational transfer: § Translation begins of a free ribosome in the cytosol § A signal peptide sequence is translated, which binds a signal recognition particle (SRP) 3. Targeting to cellular location Binding of SRP stops translation and directs the ribosome to the RER when it binds to a SRP receptor Translation re-starts, with the growing polypeptide moving through a channel into the lumen of the RER § Once in the RER, the signal peptide sequence is removed SRP receptor 3. Targeting to cellular location If a protein needs to be inserted into a cell membrane, it will contain a stop transfer sequence § When the stop transfer sequence comes into contact with the translocator, translation is paused. § Translocator will discharge the polypeptide into the phospholipid bilayer of the ER membrane. Signal recognition sequence Translation resumes until the polypeptide is complete. Q: Do you think the amino acids in the stop transfer sequence are polar or non-polar? The end! References Abali, Emine E; Cline, Susan D; Franklin, David S; Viselli, Susan M. Lippincott Illustrated Reviews: Biochemistry (Lippincott Illustrated Reviews Series) (p. 105). Wolters Kluwer Health Boron, W. and Boulpaep, E. Medical Physiology (3rd ed). Elsevier Alberts et al. Molecular Biology of the Cell. Garland Science. Betts et al. Anatomy and Physiology (2ed). OpenStax Images: § Kcneuman, CC BY-SA 4.0 , via Wikimedia Commons. Retrieved from: https://upload.wikimedia.org/wikipedia/commons/7/7e/Topological_ram ifications_of_DNA_replication_and_transcription.jpg