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...

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 <https://creativecommons.org/licenses/bysa/4.0>, via Wikimedia Commons. Retrieved from: https://upload.wikimedia.org/wikipedia/commons/7/7e/Topological_ram ifications_of_DNA_replication_and_transcription.jpg