New roles of an epigenetic regulator in RNA processing are discovered, which could be targeted for cancer treatment.
The complexity by which cells regulate gene and protein expression is multifaceted ...and intricate. Regulation of 3′ untranslated region (UTR) processing of mRNA has been shown to play a critical role in development and disease. However, the process by which cells select alternative mRNA forms is not well understood. We discovered that the
Saccharomyces cerevisiae
lysine demethylase, Jhd2 (also known as KDM5), recruits 3′UTR processing machinery and promotes alteration of 3′UTR length for some genes in a demethylase-dependent manner. Interaction of Jhd2 with both chromatin and RNA suggests that Jhd2 affects selection of polyadenylation sites through a transcription-coupled mechanism. Furthermore, its mammalian homolog KDM5B (also known as JARID1B or PLU1), but not KDM5A (also known as JARID1A or RBP2), promotes shortening of
CCND1
transcript in breast cancer cells. Consistent with these results, KDM5B expression correlates with shortened
CCND1
in human breast tumor tissues. In contrast, both KDM5A and KDM5B are involved in the lengthening of
DICER1
. Our findings suggest both a novel role for this family of demethylases and a novel targetable mechanism for 3′UTR processing.
MicroRNAs (miRNAs) silence the expression of their mRNA targets mainly through promoting mRNA decay. The mechanism, kinetics and participating enzymes for miRNA-mediated decay in mammalian cells ...remain largely unclear. Combining the approaches of transcriptional pulsing, RNA-tethering, over-expression of dominant-negative mutants, and siRNA-mediated gene knockdown, we show that let-7 miRNA-induced silencing complexes (miRISCs), which contain Argonaute (Ago) and TNRC6 (also known as GW182) proteins, trigger highly rapid mRNA decay by inducing accelerated biphasic deadenylation mediated via Pan2-Pan3 and Ccr4-Caf1 deadenylase complexes followed by Dcp1-Dcp2 complex-directed decapping in mammalian cells. When tethered to mRNAs, all four human Ago proteins and TNRC6C are each able to recapitulate the two deadenylation steps. Two conserved human Ago2 phenylalanines (F470 and F505) are critical for recruiting TNRC6 to promote deadenylation. These findings indicate that promoting biphasic deadenylation to trigger mRNA decay is an intrinsic property of miRISCs.
The complexity by which cells regulate gene and protein expression is multifaceted and intricate. Regulation of 3' untranslated region (UTR) processing of mRNA has been shown to play a critical role ...in development and disease. However, the process by which cells select alternative mRNA forms is not well understood. We discovered that the
lysine demethylase, Jhd2 (also known as KDM5), recruits 3'UTR processing machinery and promotes alteration of 3'UTR length for some genes in a demethylase-dependent manner. Interaction of Jhd2 with both chromatin and RNA suggests that Jhd2 affects selection of polyadenylation sites through a transcription-coupled mechanism. Furthermore, its mammalian homolog KDM5B (also known as JARID1B or PLU1), but not KDM5A (also known as JARID1A or RBP2), promotes shortening of
transcript in breast cancer cells. Consistent with these results, KDM5B expression correlates with shortened
in human breast tumor tissues. In contrast, both KDM5A and KDM5B are involved in the lengthening of
. Our findings suggest both a novel role for this family of demethylases and a novel targetable mechanism for 3'UTR processing.
Cysteine‐rich secretory proteins (CRISPs) are widely distributed in mammals and snake venoms. They possess apparent homology but varying functions. The structure of CRISPs has remained elusive. Two ...novel members of the family, natrin and stecrisp, have been purified from Naja atra and Trimeresurus stejnegeri venoms, respectively. Their crystals diffract X‐rays to resolution limits of 2.1 and 1.6 Å, repectively, and belong to the orthorhombic system with different space groups, unit‐cell parameters and numbers of molecules per asymmetric unit. Their structures will contribute a structural basis for further functional studies of this family.
A cyclodextrin aldehyde based molecularly imprinted polymer with thermally responsive Diels-Alder (DA) linkages of grafted furan-type dienes was polymerized. The synthesized DA-MIP has dienophile ...characteristics and the specific absorption of ethyl carbamate (EC) can be switched on or off simply by thermal adjustment to 130 °C and 60 °C, respectively. The imprinting factors (
) of the MIP and rDA-MIP to EC were 6.2 and 5.0, and the selection factors (
) were 5.2 and 4.0, respectively. The restoration of the molecular target ratio was 88%, as determined by absorption and desorption experiments. The thermal restoration ratio, determined by thermal cycling experiments, was 78%. A new electrochemical sensor was prepared using the DA-MIP and its responsiveness for detecting trace amounts of EC was investigated. The results indicate that the electrode response has good affinity and excellent specific recognition performance for template molecular chemicals.
Object. To investigate the clinicopathological features, imaging findings, treatment, and prognosis of primary pulmonary lymphoepitheliomatoid-like carcinoma. Methods. The clinical data of six ...patients with primary pulmonary lymphoepithelioma-like carcinoma treated in Zhejiang Taizhou Hospital of Taizhou Enze Medical Center (Group) from May 2014 to December 2018 were summarized and analyzed. Combined with the relevant literature, the primary pulmonary lymphoepithelioma-like carcinoma was analyzed retrospectively. Results. The main manifestations of six patients were respiratory symptoms, and cough was the most common. The imaging features of six patients were mainly round-like high-density mass shadow or nodule shadow. All patients were diagnosed by pathology. Microscopically, the cancer cells were nested, with large nuclei and vacuoles and abundant lymphocyte infiltration in the tumor stroma. The positive rates of EBER, p63, CK5/6, and Ki-67 were high, and TTF-1 was negative. Five patients received surgical treatment. One patient developed brain metastasis 12 months after operation and received craniocerebral radiotherapy. The other patients did not receive radiotherapy and chemotherapy, and one patient did not receive treatment. After follow-up, four patients survived so far, the longest survival time was 82 months, one patient lost follow-up, and one patient died of lung metastasis 24 months after operation. Conclusion. Primary pulmonary lymphoepitheliomatoid-like carcinoma is a rare lung malignant tumor, whose pathogenesis is related to Epstein-Barr virus infection. The clinical manifestations are nonspecific, but with unique pathological characteristics. Surgical resection is the proper treatment for early-stage patients, and comprehensive treatment with surgery as the main treatment is suitable for late-stage patients. The prognosis is good.
The interface structure of the poly(ethylene terephthalate) (PET)/silica nanocomposites was characterized by Fourier transform infrared and solid-state nuclear magnetic resonance. Our study reveals ...that PET chains are grafted onto the surface of silica nanoparticles, and they form branched and lightly crosslinking structures during the polycondensation. Gel permeation chromatography measurements indicate that the grafted PET chains have a lower molecular weight and broader distribution. Furthermore, a model has been developed to elucidate the interaction of an entanglement network between silica and PET chains that lead to enhancements of G′, G″ and η* values of PET/2wt% silica nanocomposites.
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