Key players in regulatory RNA realm of bacteria

Precise regulation of gene expression is crucial for living cells to adapt for survival in diverse environmental conditions. Among the common cellular regulatory mechanisms, RNA-based regulators play a key role in all domains of life. Discovery of regulatory RNAs have made a paradigm shift in molecular biology as many regulatory functions of RNA have been identified beyond its canonical roles as messenger, ribosomal and transfer RNA. In the complex regulatory RNA network, riboswitches, small RNAs, and RNA thermometers can be identified as some of the key players. Herein, we review the discovery, mechanism, and potential therapeutic use of these classes of regulatory RNAs mainly found in bacteria. Being highly adaptive organisms that inhabit a broad range of ecological niches, bacteria have adopted tight and rapid-responding gene regulation mechanisms. This review aims to highlight how bacteria utilize versatile RNA structures and sequences to build a sophisticated gene regulation network.     

Two primate-specific small non-protein-coding RNAs in transgenic mice: neuronal expression, subcellular localization and binding partners

In a rare occasion a single chromosomal locus was targeted twice by independent Alu-related retroposon insertions, and in both cases supported neuronal expression of the respective inserted genes encoding small non-protein coding RNAs (npcRNAs): BC200 RNA in anthropoid primates and G22 RNA in the Lorisoidea branch of prosimians. To avoid primate experimentation, we generated transgenic mice to study neuronal expression and protein binding partners for BC200 and G22 npcRNAs. The BC200 gene, with sufficient upstream flanking sequences, is expressed in transgenic mouse brain areas comparable to those in human brain, and G22 gene, with upstream flanks, has a similar expression pattern. However, when all upstream regions of the G22 gene were removed, expression was completely abolished, despite the presence of intact internal RNA polymerase III promoter elements. Transgenic BC200 RNA is transported into neuronal dendrites as it is in human brain. G22 RNA, almost twice as large as BC200 RNA, has a similar subcellular localization. Both transgenically expressed npcRNAs formed RNP complexes with poly(A) binding protein and the heterodimer SRP9/14, as does BC200 RNA in human. These observations strongly support the possibility that the independently exapted npcRNAs have similar functions, perhaps in translational regulation of dendritic protein biosynthesis in neurons of the respective primates.     

Specific and global regulation of genes associated with the degradation of aromatic compounds in bacteria

A large number of bacteria are able to degrade aromatic carbon sources employing different strategies. All these pathways are objects of regulatory control at the level of gene expression. This includes specific control in response to the availability of the respective substrate and in many cases global control responding to other available carbon sources or to the metabolic status of the cell. Here, the regulatory proteins responsible for gene regulation are reviewed in particular in correlation to other proteins with a similar primary structure. Most common is the appearance of regulators of the LysR family; other abundant regulator types are NtrC/XyIR-type proteins, AraC/XyIS-type proteins and the IcIR-type proteins. Almost all of the regulators exert their effects as activators of gene expression with the exception of the GntR-type proteins, which are exclusively described as repressors. Factors involved in individual cases of global regulatory mechanisms are enterobacterial CAP, (p)ppGpp, Crc protein, and direct modification of a specific regulator. However, for most pathways of aromatic compound degradation, the molecular mechanisms causing global regulation are not understood.     

Small RNA biology is systems biology

During the last decade small regulatory RNA (srRNA) emerged as central players in the regulation of gene expression in all kingdoms of life. Multiple pathways for srRNA biogenesis and diverse mechanisms of gene regulation may indicate that srRNA regulation evolved independently multiple times. However, small RNA pathways share numerous properties, including the ability of a single srRNA to regulate multiple targets. Some of the mechanisms of gene regulation by srRNAs have significant effect on the abundance of free srRNAs that are ready to interact with new targets. This results in indirect interactions among seemingly unrelated genes, as well as in a crosstalk between different srRNA pathways. Here we briefly review and compare the major srRNA pathways, and argue that the impact of srRNA is always at the system level. We demonstrate how a simple mathematical model can ease the discussion of governing principles. To demonstrate these points we review a few examples from bacteria and animals.     

Carbon catabolite repression in bacteria.

Carbon catabolite repression (CCR) is a regulatory mechanism by which the expression of genes required for the utilization of secondary sources of carbon is prevented by the presence of a preferred substrate. This enables bacteria to increase their fitness by optimizing growth rates in natural environments providing complex mixtures of nutrients. In most bacteria, the enzymes involved in sugar transport and phosphorylation play an essential role in signal generation leading through different transduction mechanisms to catabolite repression. The actual mechanisms of regulation are substantially different in various bacteria. The mechanism of lactose-glucose diauxie in Escherichia coli has been reinvestigated and was found to be caused mainly by inducer exclusion. In addition, the gene encoding HPr kinase, a key component of CCR in many bacteria, was discovered recently.     

Biosynthesis of secreted ribonucleases of <Emphasis Type="Italic">Bacillus intermedius</Emphasis> and <Emphasis Type="Italic">Bacillus circulans</Emphasis> under nitrogen starvation

The level of biosynthesis of secreted guanyl-specific ribonucleases (RNases) of Bacillus intermedius (binases) and Bacillus circulans (RNases Bci) by recombinant B. subtilis strains increases under nitrogen starvation. The promoter of the binase gene carries the sequences homologous to the recognition sites of the regulatory protein TnrA, which regulates gene expression under growth limitation by nitrogen. Using the B. subtilis strain defective in protein TnrA, it has been shown that the regulatory protein TnrA is involved in the regulation of expression of the binase gene and the gene of RNase Bci. The TnrA regulation of expression of the RNase Bci gene is indirect, probably by means of the regulatory protein PucR. Thus, it has been established that at least two regulatory mechanisms activate the expression of the genes encoding the secreted RNases of spore-forming bacteria: a system of proteins homologous to the B. subtilis PhoP-PhoR, and regulation by a protein similar to the B. subtilis TnrA regulatory protein.     

Chloroplast translation regulation

Chloroplast gene expression is primarily controlled during the translation of plastid mRNAs. Translation is regulated in response to a variety of biotic and abiotic factors, and requires a coordinate expression with the nuclear genome. The translational apparatus of chloroplasts is related to that of bacteria, but has adopted novel mechanisms in order to execute the specific roles that this organelle performs within a eukaryotic cell. Accordingly, plastid ribosomes contain a number of chloroplast-unique proteins and domains that may function in translational regulation. Chloroplast translation regulation involves cis-acting RNA elements (located in the mRNA 5′ UTR) as well as a set of corresponding trans-acting protein factors. While regulation of chloroplast translation is primarily controlled at the initiation steps through these RNA-protein interactions, elongation steps are also targets for modulating chloroplast gene expression. Translation of chloroplast mRNAs is regulated in response to light, and the molecular mechanisms underlying this response involve changes in the redox state of key elements related to the photosynthetic electron chain, fluctuations of the ADP/ATP ratio and the generation of a proton gradient. Photosynthetic complexes also experience assembly-related autoinhibition of translation to coordinate the expression of different subunits of the same complex. Finally, the localization of all these molecular events among the different chloroplast subcompartments appear to be a crucial component of the regulatory mechanisms of chloroplast gene expression.     

Signal transduction and virulence regulation in human and animal pathogens

Abstract Pathogens have developed many strategies for survival in animals and humans which possess very effective defense mechanisms. Although there are many different ways, in which pathogenic bacteria solved the problem to overcome the host defense, some common features of virulence mechanisms can be detected even in phylogenetically very distant bacteria (Finlay and Falkow (1989) Microb. Rev. 6 1375–1383). One important feature is that the regulation of expression of virulence factors and the exact timing of their expression is very important for many of the pathogenic bacteria, as most of them have to encounter different growth situations during an infection cycle, which require a fast adaptation to the new situation by the expression of different factors. This review gives an overview about the mechanisms used by pathogenic bacteria to accomplish the difficult task of regulation of their virulence potential in response to environmental changes. In addition, the relationship of these virulence regulatory systems with other signal transduction mechanisms not involved in pathogenicity is discussed.     

转录因子与microRNA在基因表达调控中的功能联系及差异

转录因子和微RNA(microRNA)是最大的两类反式作用因子,它们是基因表达调控的重要调控因子.它们协调发挥调控作用,精细调控基因的表达,在细胞分化和动物生长发育过程中发挥重要的作用.随着对转录因子和microRNA研究的深入,人们发现转录因子和microRNA在基因表达调控网络中关系紧密,它们的分子作用机制有许多相似之处,两者都通过各自的顺式作用元件调控基因表达,且作用的方式类似.但转录因子和microRNA也存在不同之处,转录因子既可以激活基因表达,也可抑制基因表达,而microRNA主要是抑制基因表达.另外,转录因子调控区的复杂性一般高于microRNA的调控区域.本文综述了转录因子和microRNA的异同点,并提出了未来转录因子和microRNA的研究方向.     

细菌蛋白质磷酸化修饰研究进展

细菌蛋白质磷酸化修饰是调控细菌基因表达的一种重要方式,在细菌诸多生命活动中发挥非常关键的作用。本文系统概括了近年来细菌蛋白质磷酸化修饰的种类、双组分调控系统中磷酸化修饰调控信号传导、酪氨酸残基磷酸化修饰以及丝/苏氨酸残基磷酸化修饰等,同时对不同种类细菌蛋白质磷酸化修饰的功能进行综述,这些研究将对人类了解细菌蛋白质翻译后修饰的磷酸化调控及其与控制细菌感染的关系提供参考价值。     

Coordinating assembly of a bacterial macromolecular machine

The assembly of large and complex organelles, such as the bacterial flagellum, poses the formidable problem of coupling temporal gene expression to specific stages of the organelle-assembly process. The discovery that levels of the bacterial flagellar regulatory protein FlgM are controlled by its secretion from the cell in response to the completion of an intermediate flagellar structure (the hook-basal body) was only the first of several discoveries of unique mechanisms that coordinate flagellar gene expression with assembly. In this Review, we discuss this mechanism, together with others that also coordinate gene regulation and flagellar assembly in Gram-negative bacteria.