Biology subjects

Stepien, A.

Publications and source records attributed to Stepien, A..

3 recordsLinked to original sources

bioRxiv2018

FUS controls the processing of snoRNAs into smaller RNA fragments that can regulate gene expression

FUS is a multifunctional protein involved in many steps of RNA metabolism, including transcription, splicing, miRNA processing and replication-dependent histone gene expression. In this paper, we show for the first time that FUS binds and negatively regulates the levels of a subset of snoRNAs in cells. Scanning of available human small RNA databases revealed the existence of smaller RNA fragments that can be processed from FUS-dependent snoRNAs. Therefore, we suggest that FUS mediates the biogenesis of snoRNA-derived small RNAs, called sdRNAs. Further in silico approaches enabled us to predict putative targets of selected FUS-dependent sdRNAs. Our results indicate that sdRNAs may bind to different regions of target mRNAs as well as to noncoding transcripts and influence the posttranscriptional level or translation of these targets. SIGNIFICANCE STATEMENTRNA metabolism is orchestrated by a complex network of RNA-protein interactions and involves various classes of RNA molecules. Small nucleolar RNAs (snoRNAs) are commonly considered essential components of the ribosome biogenesis pathway. However, recent studies have revealed that snoRNAs can also be fragmented into small entities called snoRNA-derived RNAs (sdRNAs), which have been linked to multiple cancer types and thus may serve as next-generation prognostic or diagnostic biomarkers. In this paper, a multifunctional protein, FUS, was shown to be involved in the biogenesis of snoRNA-derived fragments. Furthermore, we combined bioinformatic analyses with complementary experimental approaches to elucidate the role of FUS-dependent sdRNAs in gene expression regulation. Our findings reveal the considerable regulatory potential of this new class of small noncoding RNAs.

molecular biology↗

bioRxiv2017

Risk factor profile of different clinical manifestations of cerebral small vessel disease - data from SHEF-CSVD Study.

BACKGROUNDLittle is known of the mechanisms of cerebral small vessel disease (CSVD). Both atherosclerosis or non-atherosclerotic diffuse arteriopathy are involved.\n\nMETHODSA single-center, prospective, case-control study was performed in consecutive patients with different CSVD manifestations. The study group consisted of 205 patients: 52 with lacunar stroke (LS), 20 with subcortical hemorrhagic stroke (HS), 50 with vascular dementia (VaD), 28 with vascular parkinsonism (VaP) and 55 controls (CG) free of cerebrovascular disease but with high vascular risk.\n\nRESULTSPatients with CSVD had significantly higher prevalence of vascular risk factors including hypertension, diabetes mellitus, polymetabolic syndrome and chronic kidney disease. Patients with CSVD had also significantly higher fasting blood glucose, homocysteine, fibrinogen, systolic blood pressure, IMT values and lower eGFR, albumin and HDL levels. After adjustment for age and sex, low eGFR, albumin and high levels of uric acid and fibrinogen were associated with all CSVD groups, elevated fasting glucose was related to LS and HS. In the multivariate analysiss, the independent predictors for CSVD were female sex, low albumin, high fibrinogen, fasting glucose and uric acid. Patients with LS had significantly higher IMT values comparing to other CSVD groups, patients with VaP had a trend towards higher homocysteine levels.\n\nCONCLUSIONRisk factor profile for CSVD as a whole differs from subjects with proatherogenic profile without history of cerebrovascular disease. Our results support the concept that CSVD is not homogeneous, and that unique risk factors profiles exist for different clinical manifestations of the disease.

neuroscience↗

bioRxiv2017

Risk of vascular events or death in different manifestations of cerebral small vessel disease: a 2-year follow-up study with a control group

Background and PurposeNatural course of cerebral small vessel disease (CSVD) has not yet been thoroughly studied. The aim of the single center study was to establish risk of vascular events or death in different manifestations of CSVD.\n\nMethods150 consecutive, functionally independent patients with marked MRI features of CSVD and with recent lacunar stroke (n=52, LS), 20 with deep hemorrhagic stroke (HS), 28 with vascular parkinsonism (VaP), 50 with vascular dementia (VaD) and 55 controls (CG) with high atherothrombotic risk free of cerebrovascular events were prospectively recruited and followed for 24 months.\n\nResultsMean age and sex distribution were similar in CSVD and CG but patients with CSVD were less likely to have CAD (19% vs 40%, p=0,02) and tended to have higher prevalence of diabetes (54% vs 37%, p=0,11). The risk of vascular events or death was increased in any patients with moderate to severe white matter lesions at baseline MRI (HR 2,0; 95%CI 0,85-7,2), in CSVD (4,56; 95%CI 1,3-14,9) vs CG, regardless of its clinical manifestation: LS or HS (HR 4,70; 95%CI 1,3-16,2) and VaD or VaP (HR 4,59; 95%CI 1,3-15,7).\n\nConclusionsPatients with symptomatic CSVD regardless of the clinical (acute or chronic) manifestation had more than fourfold the risk of vascular events or death in 24 months of observation compared with controls with high atherothrombotic risk free of cerebrovascular events.

neuroscience↗