The stringent response, also called stringent control, is a stress response of bacteria and plant
chloroplast
A chloroplast () is a type of membrane-bound organelle, organelle known as a plastid that conducts photosynthesis mostly in plant cell, plant and algae, algal cells. Chloroplasts have a high concentration of chlorophyll pigments which captur ...
s in reaction to amino-acid starvation,
fatty acid limitation, iron limitation, heat shock and other stress conditions and growth processes. The stringent response is signaled by the
alarmone
An alarmone is an intracellular signal molecule that is produced in bacteria, chloroplasts, and a slim minority of archaea reacting to harsh environmental factors. They regulate the gene expression at transcription level. Alarmones are produced in ...
(p)ppGpp
(p)ppGpp, guanosine pentaphosphate and tetraphosphate, also known as the "magic spot" nucleotides, are alarmones involved in the stringent response in bacteria that cause the inhibition of RNA synthesis when there is a shortage of amino acids. ...
, and modulates transcription of up to 1/3 of all genes in the cell. This in turn causes the cell to divert resources away from growth and division and toward amino acid synthesis in order to promote survival until nutrient conditions improve.
Response
In ''
Escherichia coli
''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...
'', (p)ppGpp production is mediated by the ribosomal protein L11 (''rplK'' resp. ''relC'') and the ribosome-associated (p)ppGpp synthetase I, RelA; deacylated tRNA bound in the ribosomal A-site is the primary induction signal.
RelA converts
GTP and
ATP into
pppGpp by adding the pyrophosphate from ATP onto the 3' carbon of the ribose in GTP, releasing
AMP. pppGpp is converted to
ppGpp
(p)ppGpp, guanosine pentaphosphate and tetraphosphate, also known as the "magic spot" nucleotides, are alarmones involved in the stringent response in bacteria that cause the inhibition of RNA synthesis when there is a shortage of amino acids. ...
by the ''gpp'' gene product, releasing
Pi. ppGpp is converted to
GDP
Gross domestic product (GDP) is a monetary measure of the total market value of all the final goods and services produced and rendered in a specific time period by a country or countries. GDP is often used to measure the economic performance o ...
by the ''
spoT
Spot or SPOT may refer to:
Places
* Spot, North Carolina, a community in the United States
* The Spot, New South Wales, a locality in Sydney, Australia
* South Pole Traverse, sometimes called the South Pole Overland Traverse
People
* Spot Coll ...
'' gene product, releasing pyrophosphate (
PPi).
GDP is converted to GTP by the ''ndk'' gene product. Nucleoside triphosphate (NTP) provides the Pi, and is converted to Nucleoside diphosphate (NDP).
In other bacteria, the stringent response is mediated by a variety of RelA/SpoT Homologue (RSH) proteins, with some having only synthetic, or hydrolytic or both (Rel) activities.
During the stringent response, (p)ppGpp accumulation affects the resource-consuming cell processes
replication,
transcription, and
translation
Translation is the communication of the semantics, meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The English la ...
. (p)ppGpp is thought to bind
RNA polymerase
In molecular biology, RNA polymerase (abbreviated RNAP or RNApol), or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that catalyzes the chemical reactions that synthesize RNA from a DNA template.
Using the e ...
and alter the transcriptional profile, decreasing the synthesis of translational machinery (such as
rRNA
Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosomal ...
and
tRNA
Transfer ribonucleic acid (tRNA), formerly referred to as soluble ribonucleic acid (sRNA), is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes). In a cell, it provides the physical link between the gene ...
), and increasing the transcription of biosynthetic genes. Additionally, the initiation of new rounds of replication is inhibited and the cell cycle arrests until nutrient conditions improve. Translational GTPases involved in protein biosynthesis are also affected by ppGpp, with Initiation Factor 2 (IF2) being the main target.
Chemical reaction catalyzed by RelA:
: ATP + GTP →
AMP + pppGpp
Chemical reaction catalyzed by SpoT:
: ppGpp → GDP + PPi
or
: pppGpp -> GTP + PPi
References
{{Reflist, 2
Cellular processes