Chapters 14 & 15: Regulation of Cellular Processes

levels of regulation

• regulation of gene expression occurs at different levels → control of transcription, translation and posttranslation

• there are similarities in the regulation of gene expression in organisms from different domains

  • there are many differences in chromosome organization, mRNA transcripts, signaling and cell structure

regulation of transcription initiation

• induction and repression of enzyme synthesis

  • enzymes central to metabolic processes, routinely needed by cells are encoded by housekeeping genes → constitutive genes that are continuously expressed

  • synthesis of enzymes involved in catabolic and anabolic pathways

synthesis of enzymes involved in catabolic pathways

• often inducible and are only expressed when needed

• inital substrate of the pathway is usually the inducer

• induction increases the amount of mRNA encoding the enzymes

synthesis of enzymes involved in anabolic pathway

• often repressible and expressed when biosynthesis of the end product is needed

• the end product of the pathway usually acts as a corepressor

• repression decreases the amount of mRNA encoding the enzyme

gene expression and regulatory mechanism: bacteria

transcription → GENE

• genetic regulatory proteins can bind to the DNA and control whether or not transcription begins

• binding of a metabolic to a riboswitch in mRNA can cause premature termination of transcription

translation → mRNA

• translational repressor proteins can bind to the mRNA and prevent translation from starting

• binding of a metabolite to a riboswitch in mRNA can block translation

posttranslation → PROTEIN

• small molecules can bind to a protein and affect its function

  • feedback inhibition, in which the product of a metabolic pathway inhibits the first enzyme in the pathway

• structure and function of a protein can be altered by covalent changes to the protein → can be reversible or irreversible = posttranslational modifications

→ FUNCTIONAL PROTEIN

gene expression and regulatory mechanism: archaea

transcription → GENE

• genetic regulatory proteins can bind to the DNA and control whether or not transcription begins

• compaction level of chromatin may influence transcription

translation → mRNA

• antisense RNA can bind to mRNA and control whether or not translation begins

posttranslation → PROTEIN

• feedback inhibition and covalent modifications may regulation protein function

→ FUNCTIONAL PROTEIN

gene expression and regulatory mechanism: eukarya

transcription → GENE

• regulatory transcription factors may activate or inhibit transcription

• compaction level of chromatin influences transcription

• DNA methylation inhibits transcription

RNA processing → pre-mRNA

• alternative splicing alters exon choices

• RNA editing alters the base sequence of mRNAs

translation → mRNA

• may be regulated by the phosphorylation of translational initiation factors

• may be regulated by proteins that bind to the 5’ end of the mRNA

• RNA can bind mRNA and control whether or not translation begins

• mRNA stability may be influenced by RNA binding proteins

posttranslation → PROTEIN

• feedback inhibition and covalent modifications may regulate protein function

FUNCTIONAL PROTEIN

control of transcription initiation by regulatory proteins

• negative transcriptional control

• positive transcriptional control

• repressor proteins

• activator proteins

• lactose operons

negative transcriptional control

occurs when a repressor protein inhibits initiation of transcripition

positive transcriptional control

occurs when activator protein promotes initiation of transcripition

repressor proteins

bind to the operator, a region of DNA overlapping or downstream of the promoter, and block RNA polymerase binding

• in inducible systems: active until bound to the inducer (binding of inducer inactivates the repressor)

• in repressible systems: inactive until bound to the corepressor (binding of corepressor activates the repressor)

activator proteins

bind activator binding sites, often upstream of the promoter

operon

in bacteria, a set of related structural genes controlled by a single operator and promoter

lactose operon

negative transcriptional control of inducible genes

example of negative regulation of an inducible gene

• encodes genes for the catabolism of lactose

• binding of the lac repressor to the lac operators bends the DNA and inhibits RNA polymerase binding or blocks the movement of RNA polymerase

lac repressor

• inactivated by binding the inducer, allolactose → derivative of lactose

• presence of lactose induces expression of the lac operon by inhibiting repressor binding

lac operon

regulated by catabolite activator protein (CAP), part of a global regulatory system

protein synthesis: operon and negative control

• operon: consists of a group of structural genes that are under the control of a single operator

• negative control: exists if the operator prevents the RNA polymerase from transcribing the structural genes

tryptophan operson

• negative transcriptional control of repressible genes

• encodes genes for the synthesis of tryptophan → excellent example of a repressible operon

• trp operon is expressed unless the trp repressor binds its corepressor, tryptophan, the end product of the pathway

  • controlled at the level of transcription elongation through attenuation

arabinose operon

• transcriptional control by a protein that acts both positively and negatively

• ara operon encodes genes for the catabolism of arabinose

  • when arabinose is absent → the ara operon is repressed by the interaciton of two AraC molecules at the operators

  • when arabinose is present → this interaction is prevented and the AraC molecules stimulate expression

regulation of transcription elongation

• attenuation

• regulation of translation

  • posttranslational regulation

attenuation

• 2 decision points for regulating transcription of anabolic pathways:

  • initiation of transcription

  • continuation of transcription

• regulated continuation of transcription

• only occur in prokaryotes where transcription/translation are simultaneous

regulation of translation by riboswitches

the binding of effector molecules changes the folding of the mRNA to inhibit ribosomal binding and initiation of translation

regulation of translation by small RNA molecules

• small RNAs (sRNAs): called noncoding RNAs (ncRNAs) are involved in regulating cellular processes by directly pairing with mRNAs

  • one kind of sRNA is antisense RNA, complementary to the leader sequence of an mRNA molecule and binds to it → thereby blocking translation

riboswitches or sensory RNAs

found in leader regions and control translation due to folding pattern change when effector molecules bind

posttranslational regulation

through allosteric control or covalent modification are forms of posttranslational regulation

• covalent modification can be reversible (phosphorylation) or irreversible (proteolysis)

global regulatory systems

affect many genes and pathways allowing for both independent regulation of operons and cooperation of operons

• regulon

• modulon

• stimulon

regulon

group of genes or operons controlled by a common regulatory protein

modulon

more complex and has a common regulatory protein that controls an operon network, individual operons are controlled separately as well

stimulon

regulatory system in which all operons respond together to an environmental stimulus

mechanisms used for global regulation

• bacteria produce many different sigma factors → each enables RNA polymerase to recognized and bind to specific promoters

• alternate sigma factors available to RNA polymerase alter gene expression

sporulation

complex process that is controlled at several levels through phosphorelay, transcription factors, posttranslational modifications, and alternate sigma factors

sporulation in Bacillus subtilis

under certain envrionmental stimuli, a response regulator protein, Spo0A, alters the expression over 500 genes → alternate sigma factors that differentially control gene expression in the forespore and mother cell

regulation of the lac operon by the lac repressor and CAP

• E. coli grows in a medium containing both glucose and lactose, it uses glucose until the sugar is exhausted

  • after a short lag, growth resumes at a slower rate with lactose as the carbon source

• if glucose is absent and lactose is present

  • inducer allolactose will bind to and inactivate the lac repressor protein → CAP will be in the active form and transcription will proceed

• if glucose and lactose are in short supply

  • CAP binds to the lac promoter, transcription will be inhibited by the presence of the repressor protein