Transfer-messenger RNA - Revision history

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	[[Category:RNA]]		[[Category:RNA]]
	[[Category:Molecular biology]]		[[Category:Molecular biology]]
			<gallery>
			File:157-TransferMessengerRNA_3iyr_composite.tif\|Transfer-messenger RNA composite structure
			File:tRNAmRNAtmRNAComparison.png\|Comparison of tRNA, mRNA, and tmRNA
			File:EsccolitmRNA2009.png\|Escherichia coli tmRNA structure
			File:TDLcartoonstructure.png\|Transfer-messenger RNA TDL cartoon structure
			File:SmpBcartoonstructure.png\|SmpB protein cartoon structure
			File:Transtranslation.png\|Transfer-messenger RNA translation process
			File:ssraHistory2.jpg\|History of ssrA gene discovery
			File:Secondary_structure_models_for_mt-tmRNAs..jpg\|Secondary structure models for mitochondrial tmRNAs
			File:Processing_of_two-piece_mt-tmRNA..jpg\|Processing of two-piece mitochondrial tmRNA
			</gallery>

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	~~'''~~Transfer-messenger RNA''' ('''tmRNA'''), also known as '''10Sa RNA''' or '''SsrA RNA''', is a bacterial RNA molecule with dual function in [[protein synthesis]] and [[RNA degradation]]. It is found in many [[bacteria]] and some [[organelle]]s, and it plays a crucial role in rescuing [[ribosomes]] stuck on damaged or incomplete [[mRNA]] molecules. The tmRNA is part of the [[trans-translation]] system, which helps in the recycling of stalled ribosomes and tagging of incomplete polypeptides for degradation.		== Transfer-messenger RNA ==

	==Structure ~~and Function==~~		[[File:157-TransferMessengerRNA_3iyr_composite.tif\|thumb\|Structure of transfer-messenger RNA]]
	~~The tmRNA molecule is unique because it possesses properties~~ of ~~both [[~~transfer ~~RNA]] (tRNA) and [[~~messenger RNA]] (mRNA). It has a tRNA-like domain (TLD) that is charged with an [[amino acid]] (usually alanine) and an mRNA-like domain that encodes a short peptide tag. This tag is used to mark proteins for degradation that are produced from damaged mRNA.

	~~During~~ trans-translation, ~~the tmRNA enters the~~ [[~~A site~~]] ~~of a~~ stalled ~~ribosome. The TLD is recognized as a tRNA, allowing the ribosome to add the alanine to the nascent polypeptide chain. The ribosome then shifts from the~~ damaged mRNA ~~to the mRNA-like domain of the tmRNA, continuing translation~~ and ~~eventually encoding the~~ degradation ~~tag~~.		'''Transfer-messenger RNA''' ('''tmRNA''') is a unique type of RNA molecule found in [[bacteria]] and [[archaea]]. It plays a crucial role in the process of [[trans-translation]], which rescues [[ribosomes]] stalled on damaged [[mRNA]] and tags incomplete [[polypeptides]] for degradation.

	==~~Biological Significance~~==		== Structure ==
	The tmRNA system is essential for bacterial survival, particularly under stress conditions that increase the likelihood of ribosome stalling. By rescuing stalled ribosomes and targeting incomplete proteins for degradation, tmRNA helps maintain protein homeostasis and reduces the accumulation of potentially toxic protein fragments.

	~~==Clinical Implications==~~		[[File:tRNAmRNAtmRNAComparison.png\|thumb\|Comparison of tRNA, mRNA, and tmRNA structures]]
	~~Given its critical role in bacterial survival, the tmRNA system has been explored as a target for novel~~ [[~~antibiotic]]s~~. ~~Inhibitors~~ of ~~tmRNA could potentially render bacteria unable to cope with protein synthesis stress~~, ~~leading to their death or weakened state~~, ~~making them more susceptible to the host immune system or other antibiotics.~~

	~~==Evolution==~~		The tmRNA molecule is a hybrid of [[transfer RNA]] (tRNA) and [[messenger RNA]] (mRNA). It contains a tRNA-like domain (TLD) that can be charged with an [[amino acid]], and an mRNA-like region that encodes a short peptide tag. The structure of tmRNA allows it to mimic both tRNA and mRNA, facilitating its role in trans-translation.
	The ~~presence of~~ tmRNA in a ~~wide range~~ of ~~bacteria~~ and ~~its absence in eukaryotes suggest~~ that ~~it is~~ an ~~ancient mechanism~~. ~~Its conservation across diverse bacterial species underscores~~ its ~~fundamental~~ role in ~~bacterial physiology~~.

	==~~Research Directions~~==		== Function ==
	Research on tmRNA continues to uncover its intricacies, including its interaction with other cellular components, its regulation, and its variation across different bacterial species. Understanding these aspects could provide insights into bacterial adaptation and lead to the development of new antibacterial strategies.

	==~~See Also~~==		[[File:EsccolitmRNA2009.png\|thumb\|tmRNA in action within a bacterial cell]]

			In the process of trans-translation, tmRNA, along with the protein [[SmpB]], binds to stalled ribosomes. The tRNA-like domain of tmRNA enters the ribosome's A site, allowing the ribosome to switch from the defective mRNA to the mRNA-like region of tmRNA. This results in the addition of a peptide tag to the nascent polypeptide, marking it for degradation by cellular proteases.

			== Mechanism of Action ==

			[[File:TDLcartoonstructure.png\|thumb\|Cartoon structure of the tRNA-like domain of tmRNA]]
			[[File:SmpBcartoonstructure.png\|thumb\|Cartoon structure of SmpB protein]]

			The trans-translation process begins when a ribosome stalls on a defective mRNA. The tmRNA-SmpB complex recognizes the stalled ribosome and enters the A site. The ribosome then shifts to the mRNA-like region of tmRNA, which encodes a short peptide sequence. This sequence is translated, and the resulting tagged polypeptide is released and targeted for degradation.

			== Evolutionary Significance ==

			[[File:Transtranslation.png\|thumb\|Diagram of the trans-translation process]]

			The presence of tmRNA in both bacteria and archaea suggests that it is an ancient and conserved mechanism for dealing with stalled ribosomes. The ability to rescue stalled ribosomes and degrade incomplete proteins is crucial for maintaining cellular homeostasis and protein quality control.

			== History of Discovery ==

			[[File:ssraHistory2.jpg\|thumb\|Historical timeline of tmRNA research]]

			The discovery of tmRNA dates back to the late 1980s and early 1990s, when researchers identified a novel RNA molecule with properties of both tRNA and mRNA. Subsequent studies revealed its role in trans-translation and its importance in cellular processes.

			== Mitochondrial tmRNA ==

			[[File:Secondary_structure_models_for_mt-tmRNAs..jpg\|thumb\|Secondary structure models for mitochondrial tmRNAs]]
			[[File:Processing_of_two-piece_mt-tmRNA..jpg\|thumb\|Processing of two-piece mitochondrial tmRNA]]

			In some [[mitochondria]], a variant of tmRNA exists, known as mitochondrial tmRNA (mt-tmRNA). These molecules have adapted to the unique environment of the mitochondrion and play a similar role in rescuing stalled ribosomes within this organelle.

			== Related Pages ==

			* [[Ribosome]]
	* [[Protein synthesis]]		* [[Protein synthesis]]
	* [[~~Ribosome~~]]		* [[RNA]]
	* [[~~Transfer RNA~~]]		* [[Proteolysis]]
	* [[Messenger RNA]]
	* [[Protein degradation]]		== References ==

			{{Reflist}}

	[[Category:RNA]]		[[Category:RNA]]
	[[Category:Molecular biology]]		[[Category:Molecular biology]]
	~~[[Category:Microbiology]]~~

	~~{{Template:Genetics-stub}}~~
	~~{{Template:Microbiology-stub}}~~
	~~{{Template:Medicine-stub}}~~

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2024-03-22T11:58:45Z

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'''Transfer-messenger RNA''' ('''tmRNA'''), also known as '''10Sa RNA''' or '''SsrA RNA''', is a bacterial RNA molecule with dual function in [[protein synthesis]] and [[RNA degradation]]. It is found in many [[bacteria]] and some [[organelle]]s, and it plays a crucial role in rescuing [[ribosomes]] stuck on damaged or incomplete [[mRNA]] molecules. The tmRNA is part of the [[trans-translation]] system, which helps in the recycling of stalled ribosomes and tagging of incomplete polypeptides for degradation.

==Structure and Function==
The tmRNA molecule is unique because it possesses properties of both [[transfer RNA]] (tRNA) and [[messenger RNA]] (mRNA). It has a tRNA-like domain (TLD) that is charged with an [[amino acid]] (usually alanine) and an mRNA-like domain that encodes a short peptide tag. This tag is used to mark proteins for degradation that are produced from damaged mRNA.

During trans-translation, the tmRNA enters the [[A site]] of a stalled ribosome. The TLD is recognized as a tRNA, allowing the ribosome to add the alanine to the nascent polypeptide chain. The ribosome then shifts from the damaged mRNA to the mRNA-like domain of the tmRNA, continuing translation and eventually encoding the degradation tag.

==Biological Significance==
The tmRNA system is essential for bacterial survival, particularly under stress conditions that increase the likelihood of ribosome stalling. By rescuing stalled ribosomes and targeting incomplete proteins for degradation, tmRNA helps maintain protein homeostasis and reduces the accumulation of potentially toxic protein fragments.

==Clinical Implications==
Given its critical role in bacterial survival, the tmRNA system has been explored as a target for novel [[antibiotic]]s. Inhibitors of tmRNA could potentially render bacteria unable to cope with protein synthesis stress, leading to their death or weakened state, making them more susceptible to the host immune system or other antibiotics.

==Evolution==
The presence of tmRNA in a wide range of bacteria and its absence in eukaryotes suggest that it is an ancient mechanism. Its conservation across diverse bacterial species underscores its fundamental role in bacterial physiology.

==Research Directions==
Research on tmRNA continues to uncover its intricacies, including its interaction with other cellular components, its regulation, and its variation across different bacterial species. Understanding these aspects could provide insights into bacterial adaptation and lead to the development of new antibacterial strategies.

==See Also==
* [[Protein synthesis]]
* [[Ribosome]]
* [[Transfer RNA]]
* [[Messenger RNA]]
* [[Protein degradation]]

[[Category:RNA]]
[[Category:Molecular biology]]
[[Category:Microbiology]]

{{Template:Genetics-stub}}
{{Template:Microbiology-stub}}
{{Template:Medicine-stub}}