Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The spatial and temporal patterns of expression and content of bFGF during postnatal development of the retina were established in C57BL/6J mice. Western blot analysis, using an anti-rodent bFGF antibody, shows multiple molecular weights of 18, 20.5, and 22 kDa of bFGF protein isolated from the adult retina. A bioassay indicates that this putative basic fibroblast growth factor (bFGF) stimulates proliferation of BALB/c 3T3 fibroblasts in a dose-dependent manner identical to an authentic bFGF standard. Immunocytochemistry reveals that bFGF immunoreactivity is located primarily in the immature photoreceptors during postnatal development and is associated with the photoreceptor outer segment/interphotoreceptor matrix complex in the adult retina. bFGF mRNA expression pattern and levels were evaluated using mouse bFGF riboprobes with in situ hybridization and quantitative ribonuclease protection assay. bFGF mRNA expression is not detectable in the retina until Postnatal Day 10 (P10), although high levels of bFGF mRNA signals were consistently observed in astrocytes in the optic disc at all postnatal ages examined. From P10 to the adult stage, bFGF mRNA was localized mainly to the photoreceptor inner segments, and the bFGF mRNA levels were approximately the same at P10 and in the adult retina. The patterns of retinal bFGF expression and content during normal development established above were compared to these parameters in the retina of rd (C57BL/6J rd/rd), a spontaneous mouse mutant in which photoreceptors degenerate shortly after birth. More bFGF immunoreactivity was detected in the outer retina during photoreceptor degeneration than was present in normal photoreceptors at equivalent ages. Densitometry measurements indicate that the level of immunoreactivity is 56% to 1.8-fold higher in rd than in the normal retina between P6 and P10, respectively. This is at least partially due to elevated bFGF mRNA expression in rd retinas during photoreceptor degeneration. In situ hybridization showed more intense bFGF mRNA hybridization signals in rd photoreceptors from P10 to P15, and RNase protection assay demonstrated much higher hybridization signals in rd retinas from P6 to P10 than in the normal retinas at these stages. More bFGF mRNA hybridization signals were also present in some cells in the inner nuclear layer following photoreceptor cell death in the rd retina but were only weakly evident in the inner nuclear layer in the normal adult retina. These results provide the first evidence that a naturally occurring neuronal degeneration is accompanied by elevated expression of bFGF in degenerating neurons prior to cell death.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Basic fibroblast growth factor in retinal development: differential levels of bFGF expression and content in normal and retinal degeneration (rd) mutant mice. 775 Jun 36

The release of GnRH peptide from neuroterminals in the median eminence increases during postnatal development. We were interested in determining the biosynthetic component contributing to the regulation of GnRH decapeptide levels, and ascertaining the molecular mechanism for these changes. Male and female C57bl/6 mice, from embryonic day (E)16 through postnatal day (P)60, were killed, and the preoptic area-anterior hypothalamus was dissected out. Cytoplasmic and nuclear RNA were extracted separately. Levels of GnRH messenger RNA (mRNA) and primary transcript were quantitated in individual preoptic area-anterior hypothalamus cytoplasmic and nuclear fractions, respectively, by ribonuclease protection assays. Serum LH levels were assayed by RIA. GnRH mRNA levels in the cytoplasm increased gradually and significantly during postnatal development in both males and females, reaching a peak at P55 in females and P40 in males. GnRH primary transcript levels in the nucleus, an index of GnRH gene transcription, changed in a completely different manner developmentally, and they differed between male and female mice. GnRH primary transcript levels in males were quite low until P5, when they underwent an increase of approximately 4-fold, between P5 and P7. They continued to increase through P15, at which time they reached adult levels. In females, GnRH primary transcript levels were high at E16, decreased to a nadir at P5, and then underwent an increase of approximately 5-fold to P7, which were comparable with adult levels. The large and sexually dimorphic changes in GnRH primary transcript between E16 and P7, in the absence of similar changes in GnRH mRNA, suggest that differential mechanisms, such as gene transcription and mRNA stability, play a role in determining levels of GnRH mRNA at different stages of development.
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PMID:Mechanisms for the regulation of gonadotropin-releasing hormone gene expression in the developing mouse. 1021 81

Thyroid hormone (TH) plays a critical role in normal cerebellar development. However, the molecular mechanisms of TH action in the developing cerebellum are not fully understood. This action could be exerted in part through brain-derived neurotropic factor (BDNF), as cerebellar BDNF messenger RNA (mRNA) expression is lower, and replacement of BDNF partially reverses the abnormal neurogenesis in the hypothyroid rat. The rat BDNF gene consists of four noncoding exons (exons I-IV), each of which is linked to a different promoter, and a protein-coding exon (exon V). To study promoter-specific regulation of the BDNF gene by TH, ribonuclease protection assay of each exon mRNA was performed using total developing rat cerebellar RNA. During cerebellar development, all exon mRNAs were detected, but with different expression patterns; among noncoding exon mRNAs, exon II mRNA was the most abundant. Daily TH replacement induced a 3-fold increase in exon II mRNA on postnatal day (P) 15. On P30, exon II mRNA was still much greater in the TH-replaced animal. Exon I mRNA was detected on P2 and P7. However, in contrast to exon II mRNA, TH treatment suppressed the expression of exon I mRNA on P2. Exon III and IV mRNAs were not detected on P2 and P7, but small amounts were observed starting on P15 in TH-replaced animals. They were not detected by P30 in hypothyroid animals. In contrast, in the cerebral cortex, although all exons are differentially regulated during development, the expression of each mRNA was not significantly altered by TH. These results indicate that TH regulates BDNF gene expression in a promoter-, developmental stage-, and brain region-specific manner, which may play an important role in region- and stage-specific regulation of brain development by TH.
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PMID:Promoter-specific regulation of the brain-derived neurotropic factor gene by thyroid hormone in the developing rat cerebellum. 1046 64

These studies were performed to determine the developmental expression pattern of neurotrophic factor (NTF: nerve growth factor (betaNGF), brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF), neurotrophin-3 (NT-3) and NT-4 mRNA and NGF, NT-3 and NT-4 protein in the urinary bladder of the postnatal Wistar rat. It was hypothesized that NTFs may contribute to the development of the spinobulbospinal micturition reflex that represents the adult micturition pattern. Changes in NTF mRNA or protein expression in the urinary bladder at the time of development of the mature micturition reflex (postnatal days (P) 16-18) may suggest an involvement of target-derived NTFs in this maturation process. Developmental ages, prior to (P5, P10, P15) or following (P20, P30, adult P90) the development of the spinobulbospinal micturition reflex were selected and the urinary bladder was analyzed for levels of neurotrophic factor mRNA or protein. Results from ribonuclease protection assays demonstrated a similar developmental pattern among each neurotrophic factor examined. Neurotrophic factor mRNA levels increased by P10 and reach a maximum by P15. Subsequently, NTF mRNA levels declined to adult levels that were less than the earliest postnatal time examined (P5). NTF mRNA expression was significantly (p</=0.05-0.001) greater at P10, P15, P20 and P40 (NT-4 mRNA) compared to adult levels for each NTF examined except GDNF mRNA. In general, NGF, NT-3 and NT-4 urinary bladder protein levels in early postnatal development, as determined by ELISA, were similar when compared to the corresponding mRNA expression. Differences in the correlation between NT-3 and NT-4 mRNA and protein expression were demonstrated in the adult urinary bladder where significantly (p</=0. 001) greater levels of protein were revealed despite relatively low abundance of NT-3 and NT-4 mRNA. The developmental expression pattern (maximum expression at the second to third postnatal week) of NTFs in the urinary bladder is consistent with a potential role in the development of the spinobulbospinal reflex. Relatively high expression of NT-3 and NT-4 protein in the adult urinary bladder suggests a potential importance of these factors in the adult lower urinary tract.
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PMID:Developmental expression of urinary bladder neurotrophic factor mRNA and protein in the neonatal rat. 1067 71

In Arabidopsis, micro (mi)RNAs and trans-acting (ta-si)RNAs synthesized directly or indirectly through the DICER-LIKE-1 (DCL1) ribonuclease have roles in patterning and hormonal responses, while DCL2,3,4-dependent small-interfering (si)RNAs are mainly involved in silencing of transposable elements and antiviral defense. Viral suppressors of RNA silencing (VSRs) produced by phytoviruses to counter plant defense may perturb plant developmental programs because of the collision of their inhibitory effects with the regulatory action of endogenous miRNAs and ta-siRNAs. This could explain the similar developmental aberrations displayed by Arabidopsis miRNA/ta-siRNA pathway mutants, including dcl1, and by some VSR-expressing plants. Nonetheless, the molecular bases for these morphological aberrations have remained mysterious, and their contribution to viral disease symptoms/virulence unexplored. The extent of VSR inhibitory actions to other types of endogenous small RNAs remains also unclear. Here, we present an in-depth analysis of transgenic Arabidopsis expressing constitutively HcPro, P19 and P15, three unrelated VSRs. We show that VSR expression has comparable, yet modest effects on known miRNA and ta-siRNA target RNA levels, similar to those observed using an hypomorphic dcl1 mutation. However, by combining results of transcriptome studies with deep-sequencing data from immuno-precipitated small RNAs, additional, novel endogenous targets of miRNA and ta-siRNA were identified, unraveling an unsuspected complexity in the origin and scope-of-action of these molecules. Other stringent analyses pinpointed misregulation of the miR167 target AUXIN RESPONSE FACTOR 8 (ARF8) as a major cause for the developmental aberrations exhibited by VSR transgenic plants, but also for the phenotypes induced during normal viral infection caused by the HcPro-encoding Turnip mosaic virus (TuMV). Neither RNA silencing, its suppression by VSRs, nor the virulence/accumulation of TuMV was altered by mutations in ARF8. These findings have important implications for our understanding of viral disease symptoms and small RNA-directed regulation of plant growth/development.
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PMID:Misregulation of AUXIN RESPONSE FACTOR 8 underlies the developmental abnormalities caused by three distinct viral silencing suppressors in Arabidopsis. 2714 83

The rnpB gene encodes for the RNA subunit of the catalytic ribonuclease RNase P and is present in all bacteria and has both conserved and highly variable sequence regions. Determination of rnpB in 35 Mycobacterium spp. showed species specific sequences for all species except the Mycobacterium tuberculosis complex (four species). High sequence variation was seen in the P3, P15 and P19 regions of suggested secondary structures of the corresponding RNase P RNA molecules. Phylogenetic analysis showed that rnpB gave similar tree topologies as 16S rRNA and hsp65 genes. A combined analysis of the three genes increased the number of nodes with significant support from 10 to 19. The results indicate that rnpB is useful for phylogenetic studies and is a possible target for identification and detection of Mycobacterium spp.
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PMID:Differentiation and phylogenetic relationships in Mycobacterium spp with special reference to the RNase P RNA gene rnpB. 2496 95