Cell cycle control: many ways to skin a cat

Thirty exponential cell divisions after fertilization would produce the number of cells in a baby mouse, but would not make a mouse. Sophisticated controls govern the cell cycle during development. These controls appear to play a central role in sculpting biological form. Rapid advances in our understanding of the machinery that drives the cell cycle provide a foundation for investigation of the molecular nature of cell cycle control in development. In this article, I emphasize that the design of the cell cycle machinery provides numerous inputs for regulation. I hope that the emphasis I have chosen will avert a tendency towards a narrow perception of cell cycle control.     

Conservation biology: the many ways to protect biodiversity

Protecting hotspots of marine species richness may not be an effective strategy to conserve biodiversity because these sites do not coincide with hotspots of functional and phylogenetic diversity.     

miRNA在调控皮肤和毛囊发育中的作用

表皮发生和毛囊的周期性再生涉及一系列基因的激活和沉默。近年来的研究表明, miRNA的表达谱在表皮和毛囊组织中存在组织特异性, 在毛囊周期性发育中存在阶段特异性。大量miRNA参与表皮和毛囊的发生, 色素的沉着以及毛囊的周期性发育过程, 不同类型细胞中的miRNA通过与信号通路和调控因子相互作用形成了一个全方位、多层次的网络调控系统。文章综述了miRNA调控表皮内稳态和毛囊周期性发育的一些研究 进展, 旨在丰富miRNA参与的基因调控网路的研究, 进而为人工调控miRNA进行疾病治疗和分子育种提供 帮助。     

The many ways to cleave hyaluronan

Hyaluronan is being used increasingly as a component of artificial matrices and in bioengineering for tissue scaffolding. The length of hyaluronan polymer chains is now recognized as informational, involving a wide variety of size-specific functions. Inadvertent scission of hyaluronan can occur during the process of preparation. On the other hand, certain size-specific hyaluronan fragments may be desirable, endowing the finished bioengineered product with specific properties. In this review, the vast arrays of reactions that cause scission of hyaluronan polymers is presented, including those on an enzymatic, free radical, and chemical basis.     

miRNA biogenesis and inherited disorders: clinico-molecular insights

MicroRNAs (miRNAs) play vital roles in the regulation of gene expression, a process known as miRNA-induced gene silencing. The human genome codes for many miRNAs, and their biogenesis relies on a handful of genes, including DROSHA, DGCR8, DICER1, and AGO1/2. Germline pathogenic variants (GPVs) in these genes cause at least three distinct genetic syndromes, with clinical manifestations that range from hyperplastic/neoplastic entities to neurodevelopmental disorders (NDDs). Over the past decade, DICER1 GPVs have been shown to lead to tumor predisposition. Moreover, recent findings have provided insight into the clinical consequences arising from GPVs in DGCR8, AGO1, and AGO2. Here we provide a timely update with respect to how GPVs in miRNA biogenesis genes alter miRNA biology and ultimately lead to their clinical manifestations.     

Alternative miRNA biogenesis pathways and the interpretation of core miRNA pathway mutants

Since the establishment of a canonical animal microRNA biogenesis pathway driven by the RNase III enzymes Drosha and Dicer, an unexpected variety of alternative mechanisms that generate functional microRNAs have emerged. We review here the many Drosha-independent and Dicer-independent microRNA biogenesis strategies characterized over the past few years. Beyond reflecting the flexibility of small RNA machineries, the existence of noncanonical pathways has consequences for interpreting mutants in the core microRNA machinery. Such mutants are commonly used to assess the consequences of "total" microRNA loss, and indeed, they exhibit many overall phenotypic similarities. Nevertheless, ongoing studies reveal a growing number of settings in which alternative microRNA pathways contribute to distinct phenotypes among core microRNA biogenesis mutants.     

The many ways to open the gate to colon cancer

Comment on: Amos-Landgraf JM, et al. Proc Natl Acad Sci USA 2012; 109:2060-5.     

Inhibition of antigen presentation by Brucella: many more than many ways

Brucella infection activates the immune system and favors the differentiation of CD4⁺ and CD8⁺ T cells. To persist during a long time inside macrophages evading immune surveillance of these T cells the pathogen must exploit different evasion strategies. We review the mechanisms whereby Brucella, through TLR signaling, inhibits MHC class I and II antigen presentation, allowing infected macrophages to become effective niches for Brucella survival.     

Two ways to skin a cat: acyldepsipeptides antibiotics can kill bacteria through activation or inhibition of ClpP activity

Infection by Mycobacterium tuberculosis (Mtb) has had a devastating effect on the world population. Acyldepsipeptide antibiotics (ADEPs) are known to kill some bacteria by over activating the bacterial ClpP peptidase. ADEP antibiotics also target Mtb, with the assumption that uncontrolled ADEP‐activated proteolysis by ClpP is the common mode of killing. In this issue of Molecular Microbiology, Famulla, et al. now show that ADEP's effectiveness in mycobacteria is likely due to inhibition of ClpP‐dependent protease activity rather than activation. This finding of how the same antibiotic can kill bacteria by either inhibiting or activating proteases illustrates the utility of targeting these enzymes for sorely needed new antibiotics.     

UsnRNP biogenesis: mechanisms and regulation

Macromolecular complexes composed of proteins or proteins and nucleic acids rather than individual macromolecules mediate many cellular activities. Maintenance of these activities is essential for cell viability and requires the coordinated production of the individual complex components as well as their faithful incorporation into functional entities. Failure of complex assembly may have fatal consequences and can cause severe diseases. While many macromolecular complexes can form spontaneously in vitro, they often require aid from assembly factors including assembly chaperones in the crowded cellular environment. The assembly of RNA protein complexes implicated in the maturation of pre-mRNAs (termed UsnRNPs) has proven to be a paradigm to understand the action of assembly factors and chaperones. UsnRNPs are assembled by factors united in protein arginine methyltransferase 5 (PRMT5)- and survival motor neuron (SMN)-complexes, which act sequentially in the UsnRNP production line. While the PRMT5-complex pre-arranges specific sets of proteins into stable intermediates, the SMN complex displaces assembly factors from these intermediates and unites them with UsnRNA to form the assembled RNP. Despite advanced mechanistic understanding of UsnRNP assembly, our knowledge of regulatory features of this essential and ubiquitous cellular function remains remarkably incomplete. One may argue that the process operates as a default biosynthesis pathway and does not require sophisticated regulatory cues. Simple theoretical considerations and a number of experimental data, however, indicate that regulation of UsnRNP assembly most likely happens at multiple levels. This review will not only summarize how individual components of this assembly line act mechanistically but also why, how, and when the UsnRNP workflow might be regulated by means of posttranslational modification in response to cellular signaling cues.