CsrA coordinates the expression of ribosome hibernation and anti-σ factor proteins.

The Csr/Rsm system (carbon storage regulator or repressor of stationary phase metabolites) is a global post-transcriptional regulatory system that coordinates and responds to environmental cues and signals, facilitating the transition between active growth and stationary phase. Another key determinant of bacterial lifestyle decisions is the management of the cellular gene expression machinery. Here, we investigate the connection between these two processes in .

CsrA regulation via binding to the base-pairing small RNA Spot 42.

The carbon storage regulator system and base-pairing small RNAs (sRNAs) represent two predominant modes of bacterial post-transcriptional regulation, which globally influence gene expression. Binding of CsrA protein to the 5' UTR or initial mRNA coding sequences can affect translation, RNA stability, and/or transcript elongation. Base-pairing sRNAs also regulate these processes, often requiring assistance from the RNA chaperone Hfq.

Diverse Mechanisms and Circuitry for Global Regulation by the RNA-Binding Protein CsrA.

The carbon storage regulator (Csr) or repressor of stationary phase metabolites (Rsm) system of is among the most complex and best-studied posttranscriptional regulatory systems. Based on a small RNA-binding protein, CsrA and homologs, it controls metabolism, physiology, and bacterial lifestyle decisions by regulating gene expression on a vast scale. Binding of CsrA to sequences containing conserved GGA motifs in mRNAs can regulate translation, RNA stability, riboswitch function, and transcript elongation.

CsrA-Mediated Translational Activation of Expression in Escherichia coli.

The sequence-specific RNA-binding protein CsrA is the central component of the conserved global regulatory Csr system. In , CsrA regulates many cellular processes, including biofilm formation, motility, carbon metabolism, iron homeostasis, and stress responses. Such regulation often involves translational repression by CsrA binding to an mRNA target, thereby inhibiting ribosome binding.

Posttranscription Initiation Control of Gene Expression Mediated by Bacterial RNA-Binding Proteins.

RNA-binding proteins play vital roles in regulating gene expression and cellular physiology in all organisms. Bacterial RNA-binding proteins can regulate transcription termination via attenuation or antitermination mechanisms, while others can repress or activate translation initiation by affecting ribosome binding. The RNA targets for these proteins include short repeated sequences, longer single-stranded sequences, RNA secondary or tertiary structure, and a combination of these features.

Selective Inhibition of Prostasin in Human Enterocytes by the Integral Membrane Kunitz-Type Serine Protease Inhibitor HAI-2.

Mutations of hepatocyte growth factor activator inhibitor (HAI)-2 in humans cause sodium loss in the gastrointestinal (GI) tract in patients with syndromic congenital sodium diarrhea (SCSD). Aberrant regulation of HAI-2 target protease(s) was proposed as the cause of the disease. Here functional linkage of HAI-2 with two membrane-associated serine proteases, matriptase and prostasin was analyzed in Caco-2 cells and the human GI tract.

Natural Endogenous Human Matriptase and Prostasin Undergo Zymogen Activation via Independent Mechanisms in an Uncoupled Manner.

The membrane-associated serine proteases matriptase and prostasin are believed to function in close partnership. Their zymogen activation has been reported to be tightly coupled, either as a matriptase-initiated proteolytic cascade or through a mutually dependent mechanism involving the formation of a reciprocal zymogen activation complex. Here we show that this putative relationship may not apply in the context of human matriptase and prostasin.

Matriptase Complexes and Prostasin Complexes with HAI-1 and HAI-2 in Human Milk: Significant Proteolysis in Lactation.

Significant proteolysis may occur during milk synthesis and secretion, as evidenced by the presence of protease-protease inhibitor complex containing the activated form of the type 2 transmembrane serine protease matriptase and the transmembrane Kunitz-type serine protease inhibitor HAI-1. In order to identify other proteolysis events that may occur during lactation, human milk was analyzed for species containing HAI-1 and HAI-2 which is closely related to HAI-1. In addition to the previously demonstrated matriptase-HAI-1 complex, HAI-1 was also detected in complex with prostasin, a glycosylphosphatidylinositol (GPI)-anchored serine protease.

Plasminogen-Dependent Matriptase Activation Accelerates Plasmin Generation by Differentiating Primary Human Keratinocytes.

Pericellular plasmin generation, an important pathophysiological process, can be initiated and accelerated by the autoactivation of the type 2 transmembrane serine protease matriptase and subsequent activation of urokinase plasminogen activator. The link between matriptase and plasminogen was initially thought to be one-directional: from matriptase, through plasminogen activator, to plasminogen. However, in the current study, we now show that primary human keratinocytes that are undergoing calcium-induced differentiation can rapidly activate matriptase in response to serum treatment via a mechanism dependent on intracellular calcium, protein kinase C, and phosphatidylinositol 3-kinases-based signaling.

N-Glycan Branching Affects the Subcellular Distribution of and Inhibition of Matriptase by HAI-2/Placental Bikunin.

The gene product of SPINT 2, that encodes a transmembrane, Kunitz-type serine protease inhibitor independently designated as HAI-2 or placenta bikunin (PB), is involved in regulation of sodium absorption in human gastrointestinal track. Here, we show that SPINT 2 is expressed as two species of different size (30-40- versus 25-kDa) due to different N-glycans on Asn-57. The N-glycan on 25-kDa HAI-2 appears to be of the oligomannose type and that on 30-40-kDa HAI-2 to be of complex type with extensive terminal N-acetylglucosamine branching.