Timing without coding: How do long non-coding RNAs regulate circadian rhythms?

Long non-coding RNAs (lncRNAs) are a new class of regulatory RNAs that play important roles in disease development and a variety of biological processes. Recent studies have underscored the importance of lncRNAs in the circadian clock system and demonstrated that lncRNAs regulate core clock genes and the core clock machinery in mammals. In this review, we provide an overview of our current understanding of how lncRNAs regulate the circadian clock without coding a protein.

Natural antisense transcript of regulates the amplitude of the mouse circadian clock.

In mammals, a set of core clock genes form transcription-translation feedback loops to generate circadian oscillations. We and others recently identified a novel transcript at the () locus that is transcribed from the antisense strand of This transcript, is expressed rhythmically and antiphasic to mRNA, leading to our hypothesis that and mutually inhibit each other's expression and form a double negative feedback loop. By perturbing the expression of , we found that transcription, but not transcript, represses However, does not repress as knockdown led to a decrease in the level, indicating that forms a single negative feedback loop with and maintains the level of within the oscillatory range.

STK11 domain XI mutations: candidate genetic drivers leading to the development of dysplastic polyps in Peutz-Jeghers syndrome.

Peutz-Jeghers syndrome (PJS) is a rare hereditary disorder resulting from mutations in serine/threonine kinase 11 (STK11) and characterized by gastrointestinal (GI) hamartomatous polyps, mucocutaneous pigmentation, and an increased risk for specific cancers. Little is known about the genetic implications of specific STK11 mutations with regard to their role in dysplastic and malignant transformation of GI polyps. Peripheral blood genomic DNA samples from 116 Chinese PJS patients from 52 unrelated families were investigated for STK11 mutations.

Multicentric osteolysis with nodulosis and arthropathy (MONA) with cardiac malformation, mimicking polyarticular juvenile idiopathic arthritis: case report and literature review.

Unlabelled: The 'vanishing bone' syndrome multicentric osteolysis with nodulosis and arthropathy (MONA) is a rare chronic skeleton disorder caused by matrix metalloproteinase 2 (MMP2) deficiency, mimicking erosive polyarticular juvenile idiopathic arthritis. MONA is characterised by facial dysmorphism, subcutaneous fibrocollagenous nodules, carpal and tarsal osteolysis and interphalangeal joint erosions. We present the case of a 5-year-old boy with double outlet right ventricle, ventricular septal defect, coarctation of the aorta and MONA.

Mutation of membrane type-1 metalloproteinase, MT1-MMP, causes the multicentric osteolysis and arthritis disease Winchester syndrome.

The "vanishing bone" syndromes represent a group of rare skeletal disorders characterized by osteolysis and joint destruction, which can mimic severe rheumatoid arthritis. Winchester syndrome was one of the first recognized autosomal-recessive, multicentric forms of the disorder. It was originally described nearly 50 years ago in two sisters with a severe crippling osteolysis.

Loss of MMP-2 in murine osteoblasts upregulates osteopontin and bone sialoprotein expression in a circuit regulating bone homeostasis.

Multicentric osteolysis with arthropathy (MOA; MIM 605156) is an inherited osteolyses and arthritis syndrome resulting from loss of matrix metalloproteinase 2 (MMP-2). We recently demonstrated that Mmp2(-/-) mice represent a unique model for the study of the human disease, sharing many features of the human syndrome including skeletal dysplasia and defects in osteoblast behavior. We therefore sought to explore the secondary molecular effects of MMP-2 loss, which coexist with the underlying skeletal and osteoblast phenotypes.

Application of RNA-Seq transcriptome analysis: CD151 is an Invasion/Migration target in all stages of epithelial ovarian cancer.

Background: RNA-Seq allows a theoretically unbiased analysis of both genome-wide transcription levels and mutation status of a tumor. Using this technique we sought to identify novel candidate therapeutic targets expressed in epithelial ovarian cancer (EOC).

Methods: Specifically, we sought candidate invasion/migration targets based on expression levels across all tumors, novelty of expression in EOC, and known function.

IGFBP-4 tumor and serum levels are increased across all stages of epithelial ovarian cancer.

Background: We sought to identify candidate serum biomarkers for the detection and surveillance of EOC. Based on RNA-Seq transcriptome analysis of patient-derived tumors, highly expressed secreted proteins were identified using a bioinformatic approach.

Methods: RNA-Seq was used to quantify papillary serous ovarian cancer transcriptomes.

Loss of MMP-2 disrupts skeletal and craniofacial development and results in decreased bone mineralization, joint erosion and defects in osteoblast and osteoclast growth.

The 'vanishing bone' or inherited osteolysis/arthritis syndromes represent a heterogeneous group of skeletal disorders characterized by mineralization defects of affected bones and joints. Differing in anatomical distribution, severity and associated syndromic features, gene identification in each 'vanishing bone' disorder should provide unique insights into genetic/molecular pathways contributing to the overall control of skeletal growth and development. We previously described and then demonstrated that the novel autosomal recessive osteolysis/arthritis syndrome, multicentric osteolysis with arthritis (MOA) (MIM #605156), was caused by inactivating mutations in the MMP2 gene [Al Aqeel, A.