Ribosomal protein L4 regulates the 11-gene S10 operon in Escherichia coli by acting, in concert with transcription factor NusA, to cause premature transcription termination at a Rho-independent termination site in the leader sequence. This process presumably involves L4 interaction with the leader mRNA. Here, we report direct, specific, and independent binding of ribosomal protein L4 to the S10 mRNA leader in vitro. Most of the binding energy is contributed by a small hairpin structure within the leader region, but a 64-nucleotide sequence is required for the bona fide interaction. Binding to the S10 leader mRNA is competed by the 23 S rRNA L4 binding site. Although the secondary structures of the mRNA and rRNA binding sites appear different, phosphorothioate footprinting of the L4-RNA complexes reveals close structural similarity in three dimensions. Mutational analysis of the mRNA binding site is compatible with the structural model. In vitro binding of L4 induces structural changes of the S10 leader RNA, providing a first clue for how protein L4 may provoke transcription termination.Ribosomal proteins are encoded on the bacterial chromosomes in multigene operons that facilitate stoichiometric production of the more than 50 ribosomal proteins (r-proteins).
1Expression of most of these operons is translationally regulated by a single regulatory r-protein encoded by a given polycistronic mRNA. This operon-specific autogenous control mechanism is elicited when repressor r-proteins are not consumed during the assembly of ribosomal subunits. In the absence of sufficient ribosomal RNA targets, the resulting excess of "free" repressor proteins bind to their own mRNAs and block translation of the polycistronic mRNA (reviewed in Refs. 1 and 2).R-protein L4 from Escherichia coli specifically regulates the S10 operon, which codes for 11 r-proteins including L4 itself (3, 4). L4 is unique among the regulatory ribosomal proteins because it regulates not only translation but also transcription of the S10 operon mRNA. The latter form of regulation is accomplished by L4 stimulation of transcription termination at a terminator (attenuator) structure in the mRNA upstream of the initiation codon of the first gene of the operon (5). Determinants necessary for L4-mediated autogenous control are contained within a 172-nucleotide 5Ј-untranslated region of the S10 operon mRNA. This region folds into six stem-loop structures termed helices HA, HB, HC, HD, HE, and HG (Fig. 1A) (6, 7).The mRNA sequences necessary for L4-mediated transcription and translation control overlap, but are not identical (8, 9). Helix HE and the unstructured sequence immediately downstream of this hairpin are necessary for translational control, whereas helices HD and HE are required for transcriptional control (8, 10, 11). L4-stimulated transcription termination occurs within the U cluster (nt 139 -149) (9) in helix HE, which resembles a Rho-independent terminator. In vitro transcription experiments (10, 12) suggest that the transcription attenuation process i...
IntroductionToday, advantages of minimally invasive surgery, particularly video-assisted thoracoscopic thymectomy (VATS-TE) are well established. However, there is no consensus what VATS-TE strategy is optimal for treatment of autoimmune myasthenia gravis (MG) and thymoma.In this report, we show the results of 254 VATS-TE and suggest that VATS-TE combined with an additional cervical approach does not give any advantages compared to VATS-TE alone, which is equally effective, but reduces the risks of specific postoperative complications. Here, we summarize our 20-year experience in performing VATS-TE, and demonstrate their effectiveness and safety in complex treatment of MG and thymomas both in a short and in a long term.
Methods
This study was approved by the local Ethical CommitteeOriginal Article on Thoracic Surgery
Contributors to thyroid surgeryNikolai Ivanovich Pirogov (1810-1881) was a genius in the field of Russian surgery (Fig. 1). At the age of 20, at a written test to defend his Doctor of Medicine degree, he presented his understanding of the structure and function of
OBJECTIVE. The authors evaluated the role of antibodies to striated muscle and acetylcholine receptors in diagnostics of myasthenia gravis and thymoma, as well as outcomes of thymectomy and prognosis of myasthenia course. MATERIAL AND METHODS. The study investigated correlations of antibody content to striated muscles and acetylcholine receptors from the presence and size of thymoma, myasthenia in 157 patients with various pathologies of the thymus. The dynamics of antibody concentrations was followed up after thymectomy. RESULTS. Antibody titer to striated muscle depended on the presence and size of thymoma, severity of myasthenia and changed after thymectomy. Concentration of antibodies was associated with the presence of thymoma and it didn’t change after surgical treatment. Thymoma wasn’t revealed in patients who were seronegative to both antibodies. CONCLUSIONS. Seropositivity according to one of antibody could indicate the presence of thymoma, but its absence to both antibodies allowed doctors to eliminate this diagnosis. Antibodies to acetylcholine receptors are important markers of myasthenia. Monitoring of antibody titer dynamics to striated muscles after thymectomy could be useful for assessment of response to surgical treatment and prognosis of course of myasthenia.
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