Team:Jilin China/Description

Description

  • Sensing and responding to temperature is essential for survival

    There are always challenges for bacterial survival, especially to keep good living status facing fluctuations of chemical and physical parameters. The common chemical perturbations include sudden deprivation of nutrients or key metabolites and changes in surrounding pH. And the most representative physical deviation is temperature shift. But in most cases, the ambient temperature change is more essential for bacterial life cycle than chemical parameters, due to the efficiency of all cellular processes is temperature dependent, especially the expression of any given gene. Therefore, it’s indispensable for bacteria to evolve effective strategies , which can respond to temperature forwardly before the damages such as unfolded proteins or membrane rigidification occur.

  • Biological signal transduction systems that detect temperature shifts

    When it comes to the biological behavior of temperature sensing, to elicit a proper response that could coordinate the expression of temperature-relevant genes is very important. The common detecting systems in bacterial cells are based on three manners as followings:

    1. Transcriptional level

    Temperature sensing through DNA involves local DNA topological change followed by transcriptional event. For example, the thesis of transcription factorσ32 in E.Coli increases rapidly when temperature upshift, which could mediate the transcription of genes that haveσ32 -recognizing promoters. But this regulatory pathway takes some time to come into effect because the thermosensing proteins required time for expression.

    2.Post-translational level

    Unfolded or incorrect protein conformation is the most example of the consequences of temperature-induced damages. When temperature upshifts, chaperone proteins that are overexpressed can promote nascent polypeptide chains to fold into correct conformation, which is known as post-translational thermoregulation. But this process is more similar to lock the barn door after the horse was stolen, meaning cellular processes have already been altered due to temperature shifts.

    3.Translational level

    Temperature sensing also bases on many types of thermoregulatory RNA elements, also known for RNA-based thermosensors(RTs), which are located in the 5’ untranslated region(5’ UTR) of mRNA. The 5’ UTR is a part of bacterial transcript of gene but not a part of translational product. Therefore, RTs are none-coding RNA elements. These types of thermoregulation respond to temperature and modulate the translation of already existing or nascent mRNAs, which could induce altered mRNA stability and ribosome accessibility of ribosome binding site(RBS) thereby controlling the translation efficiency.

  • RNA-based thermosensors mediate more effective feed-forward controls

    What’s the feed-forward control? In engineering, it describes the disturbances are measured and accounted for before they have time to affect the system. Concerning intracellular temperature sensing, RNA-based thermosensors can not only respond to physiological temperature in direct and rapid way before temperature-induced damages occurring, but also reduce the time lag of transcriptional thermoregulation. Therefore, RNA-based thermoregulation performs in a more immediate and effective manner.

  • How do RNA-based thermosensors work?

    The translation rate of mRNAs depends on many biochemical factors. The most important examples of them are mRNA stability and ribosome-mRNA interaction.

    mRNAs are undergoing degradation induced by RNA ribonucleases while being synthesized at the same time. Therefore the translation rate is determined by the mRNA concentration when it gets equilibrium. Additionally, the translation of a mRNA starts form it’s translation initiation region(TIR), which contains RBS within Sine-Dalgarno sequence(SD sequence) and AUG start coden. The 30s ribosomal subunit can recognize and bind to SD sequence, consequently promoting the translation initiation. Thus the ribosome accessibility also plays an important role in translation process.

    But how do cis-acting RNA elements influence mRNA stability and ribosome accessibility? RNA-based thermosensors utilize a common but efficient way -- conformational change. The secondary or tertiary structure of mRNA such as stem-loops or pseudoknots could transform into different conformations at different temperatures. The mRNA molecules with different conformations have their own free energy. Since temperature can be described as the energy availability of mRNA molecules, there is very different probability to form the same conformation that could facilitate translation efficiently at different temperatures. There are two mechanisms of conformational change responding to temperature and control translation efficiency:

    1.Zipper-like mechanism

    This RNA element is in equilibrium between closed an open conformation. At low temperatures, the closed conformation hides the SD sequence by base-paring with vicinal anti-SD sequence. By contrast, stem-loop melts gradually at elevated temperature, finally resulting the full liberation of the SD sequence and start coden. This conformational change promotes the entire ribosome accessibility of RBS.

    Furthermore, the hidden region at low temperatures can also be substituted for Rnase recognition site, which could mediate the variations of mRNA stability in different Rnase accessibility.

    2. Switch-like mechanism

    Switch mode is also thought as two-state system. It consists of two mutually exclusive structures that depend on temperature shifts. These two structures have different mRNA stability and ribosome accessibility, thereby regulate the translation rate at different temperatures.

  • RNA-based thermosensors mediate more effective feed-forward controls

    What’s the feed-forward control? In engineering, it describes the disturbances are measured and accounted for before they have time to affect the system. Concerning intracellular temperature sensing, RNA-based thermosensors can not only respond to physiological temperature in direct and rapid way before temperature-induced damages occurring, but also reduce the time lag of transcriptional thermoregulation. Therefore, RNA-based thermoregulation performs in a more immediate and effective manner.