The 3' untranslated region of human Cyclin-Dependent Kinase 5 Regulatory subunit 1 contains regulatory elements affecting transcript stability

<p>Abstract</p> <p>Background</p> <p><it>CDK5R1 </it>plays a central role in neuronal migration and differentiation during central nervous system development. <it>CDK5R1 </it>has been implicated in neurodegenerative disorders and proposed as a candidate gene for mental retardation. The remarkable size of <it>CDK5R1 </it>3'-untranslated region (3'-UTR) suggests a role in post-transcriptional regulation of <it>CDK5R1 </it>expression.</p> <p>Results</p> <p>The bioinformatic study shows a high conservation degree in mammals and predicts several AU-Rich Elements (AREs). The insertion of <it>CDK5R1 </it>3'-UTR into luciferase 3'-UTR causes a decreased luciferase activity in four transfected cell lines. We identified 3'-UTR subregions which tend to reduce the reporter gene expression, sometimes in a cell line-dependent manner. In most cases the quantitative analysis of luciferase mRNA suggests that CDK5R1 3'-UTR affects mRNA stability. A region, leading to a very strong mRNA destabilization, showed a significantly low half-life, indicating an accelerated mRNA degradation. The 3' end of the transcript, containing a class I ARE, specifically displays a stabilizing effect in neuroblastoma cell lines. We also observed the interaction of the stabilizing neuronal RNA-binding proteins ELAV with the CDK5R1 transcript in SH-SY5Y cells and identified three 3'-UTR sub-regions showing affinity for ELAV proteins.</p> <p>Conclusion</p> <p>Our findings evince the presence of both destabilizing and stabilizing regulatory elements in <it>CDK5R1 </it>3'-UTR and support the hypothesis that <it>CDK5R1 </it>gene expression is post-transcriptionally controlled in neurons by ELAV-mediated mechanisms. This is the first evidence of the involvement of 3'-UTR in the modulation of <it>CDK5R1 </it>expression. The fine tuning of <it>CDK5R1 </it>expression by 3'-UTR may have a role in central nervous system development and functioning, with potential implications in neurodegenerative and cognitive disorders.</p

PENGETAHUAN IBU HAMIL TENTANG TANDA-TANDA BAHAYA KEHAMILAN PADA TRIMESTER III

Pada umumnya kehamilan berkembang dengan normal dan menghasilkan kelahiran bayi sehat cukup bulan melalui jalan lahir namun kadang-kadang tidak sesuai dengan yang diharapkan. Sulit diketahui sebelumnya bahwa kehamilan akan menjadi masalah (Prawirohardjo, 2006).Kurangnya pengetahuan ibu dan keluarga tentang kehamilan resiko tinggi dapat meningkatkan kejadian resiko tinggi pada kehamilan. Keterlambatan dalam mengenali secara dini tanda bahaya kehamilan dapat meningkatkan kejadian resiko tinggi kehamilan karena dalam keadaan kehamilan normal pun dapat secara tiba-tiba menjadi resiko tinggi (Depkes, 2009).Tanda-tanda bahaya pada kehamilan yang terjadi pada seorang ibu hamil merupakan suatu pertanda telah terjadinya suatu masalah yang serius pada ibu atau janin yang dikandungnya. Tanda-tanda bahaya ini dapat terjadi pada awal kehamilan (hamil muda) atau pada pertengahan atau pada akhir kehamilan (hamil tua) (Depkes RI, 2009). Adapun macam-macam tanda bahaya kehamilan pada trimester tiga antara lain: Perdarahan pervaginam, keluar air ketuban sebelum waktunya, demam tinggi, bengkak dikaki, muka dan tangan, sakit kepala yang hebat, gerakan janin tidak ada atau kurang (minimal 3 kali dalam 1 jam) (Azrul, 2005).Pengetahuan ibu dan keluarga tentang tanda-tanda bahaya kehamilan dapat memberikan landasan yang kuat agar terwujudnya perilaku sehat dalam menekankan upaya kesehatan promotif selama kehamilan. Di mana pengetahuan merupakan salah satu faktor predisposisi yang dapat mempengaruhi perilaku manusia, termasuk di dalamnya adalah perilaku ibu hamil dalam memanfaatkan secara optimal fasilitas pelayanan kesehatan (Notoatmodjo, 2007).Banda Ace

L'Autotrattamento nel progetto riabilitativo della sclerosi multipla. Risultati preliminari

Lo scopo di questo studio era quello di verificare la validit\ue0 di un programma di autotrattamento rispetto al \u201ctradizionale\u201d trattamento ambulatoriale, in pazienti affetti da sclerosi multipla (SM). Dai risultati ottenuti nel nostro studio, nonostante l'esiguit\ue0 della casistica, si pu\uf2 ipotizzare che l'autotrattamento, quando proposto a pazienti con SM selezionati e motivati, rappresenti, soprattutto nella fase iniziale della malattia, un valido approccio riabilitativo

Lost in HELLS: Disentangling the mystery of SALNR existence in senescence cellular models.

Long non-coding RNAs (lncRNAs) have emerged as key regulators of cellular senescence by transcriptionally and post-transcriptionally modulating the expression of many important genes involved in senescence-associated pathways and processes. Among the different lncRNAs associated to senescence, Senescence Associated Long Non-coding RNA (SALNR) was found to be down-regulated in different cellular models of senescence. Since its release in 2015, SALNR has not been annotated in any database or public repository, and no other experimental data have been published. The SALNR sequence is located on the long arm of chromosome 10, at band 10q23.33, and it overlaps the 3' end of the HELLS gene. This investigation helped to unravel the mystery of the existence of SALNR by analyzing publicly available short- and long-read RNA sequencing data sets and RT-PCR analysis in human tissues and cell lines. Additionally, the expression of HELLS has been studied in cellular models of replicative senescence, both in silico and in vitro. Our findings, while not supporting the actual existence of SALNR as an independent transcript in the analyzed experimental models, demonstrate the expression of a predicted HELLS isoform entirely covering the SALNR genomic region. Furthermore, we observed a strong down-regulation of HELLS in senescent cells versus proliferating cells, supporting its role in the senescence and aging process

The 3' untranslated region of human contains regulatory elements affecting transcript stability-4

<p><b>Copyright information:</b></p><p>Taken from "The 3' untranslated region of human contains regulatory elements affecting transcript stability"</p><p>http://www.biomedcentral.com/1471-2199/8/111</p><p>BMC Molecular Biology 2007;8():111-111.</p><p>Published online 3 Dec 2007</p><p>PMCID:PMC2222623.</p><p></p> element (nt 2637–2687) was deleted (hatched bar) from the pGL4.71P-C6 in construct pGL4.71P-C6del by PCR. B) Luciferase activity of the two chimeric constructs in SK-N-BE, SH-SY5Y, HEK-293 and MCF-7 cell lines. Cells, transiently co-transfected with the pGL4.71P- constructs (Renilla luciferase) and the pGL3 (Firefly luciferase) vector were harvested 24 hours post-transfection. Luciferase activity of the chimeric constructs normalized as described, is represented as a percentage of the activity observed in cells transfected with pGL4.71P (defined as 100%). Means ± s.d. luciferase values were obtained from at least four independent experiments (* p < 0.01 compared with the corresponding pGL4.71P value). C) mRNA levels of the chimeric transcripts. Total RNA was extracted from the cells harvested 24 hours post-transfection, and the reporter gene mRNA levels were analyzed by RealTime PCR. mRNA levels of the chimeric reporter gene normalized as described, are represented as a percentage of the mRNA levels observed in cells transfected with pGL4.71P (defined as 100%). Means ± s.d. luciferase mRNA values were obtained from at least three independent experiments (* p < 0.01 compared with the corresponding pGL4.71P value)