Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.5 (RNase)
 17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The turnover rates of some mRNAs vary by an order of magnitude or more when cells change their growth pattern or differentiate. To identify regulatory factors that might be responsible for this variability, we investigated how cytosolic fractions affect mRNA decay in an in vitro system. A 130,000 X g supernatant (S130) from the cytosol of exponentially growing erythroleukemia cells contains a destabilizer that accelerates the decay of polysome-bound c-myc mRNA by eightfold or more compared with reactions lacking S130. The destabilizer is deficient in or absent from the S130 of cycloheximide-treated cells, indicating that it is labile or is repressed when translation is blocked. It is not a generic RNase, because it does not affect the turnover of delta-globin, gamma-globin, or histone mRNA and does not destabilize a major portion of polysomal polyadenylated mRNA. The destabilizer accelerates the turnover of the c-myc mRNA 3' region, as well as subsequent 3'-to-5' degradation of the mRNA body. It is inactivated in vitro by mild heating and by micrococcal nuclease, suggesting that it contains a nucleic acid component. c-myb mRNA is also destabilized in S130-supplemented in vitro reactions. These results imply that the stability of some mRNAs is regulated by cytosolic factors that are not associated with polysomes.
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PMID:Regulation of c-myc mRNA stability in vitro by a labile destabilizer with an essential nucleic acid component. 274 42

Activation of the c-myb gene by viral transduction or proviral insertional mutagenesis that is likely to result in the production of structurally altered myb proteins has been shown to be predominantly associated with myelomonocytic tumors. An alternative splicing event in which a portion of the intron bounded by the vE6 and vE7 exons with v-myb homology is included as an additional 363-nucleotide coding exon has recently been identified in a mouse tumor that carries a provirus-activated myb gene. This alternative splicing was hypothesized to be a tumor-specific aberrant form of 3'-myb RNA processing as a consequence of the disruption of upstream 5'-sequences by proviral insertion. However, RNA blot analyses and RNase mapping studies presented here show that a significant portion (approximately 10%) of all myb transcripts examined, whether in normal or in clonal tumor cells, contains the additional exon. Hence the alternative splicing is a hitherto unrecognized common normal event that potentially increases the diversity of the myb proteins expressed in normal tissues including thymus and spleen, as well as in tumor cells with either normal or 5'-rearranged myb alleles. The lack of change in the ratio of the two spliced products expressed from either the normal or the 5'-rearranged myb further indicates that the insertion of the unique 121 amino acids in the larger myb transcripts is not a consequence of tumor-specific activation of the mouse myb oncogene.
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PMID:Alternative internal splicing in c-myb RNAs occurs commonly in normal and tumor cells. 283 49

Two overlapping c-ets-1 cDNA clones were isolated which contained the alpha and beta genomic sequences homologous to the 5' end of v-ets not detected in the previously described c-ets RNA species or proteins. Nucleotide sequencing demonstrated that these cDNAs corresponded to the splicing of alpha and beta to a common set of 3' exons (a through F) already found in the p54c-ets-1 mRNA. They contained an open reading frame of 1,455 nucleotides which could encode a polypeptide of 485 amino acids with a predicted molecular mass of 53 kilodaltons. However, when expressed in COS-1 cells, the cDNAs directed the synthesis of a protein with an apparent molecular mass in sodium dodecyl sulfate-polyacrylamide gel electrophoresis of 68 kilodaltons, p68c-ets-1, comigrating with a protein expressed at low levels in normal chicken spleen cells. These two proteins were shown to be identical by partial digestion with protease V8. Northern (RNA) blot hybridization analysis with the p68c-ets-1 -specific sequence and RNase protection experiments showed that the corresponding mRNA was expressed in normal chicken spleen and not in normal chicken thymus or in various T lymphoid cell lines. Thus, two closely related proteins, having distinct amino-terminal parts, are generated within the same locus by alternative addition of different 5' exons, alpha and beta or I54, respectively, onto a common set of 3' exons (a to F). Finally, we demonstrate that an aberrant splicing event between a cryptic splice donor site in c-myb exon E6 and the normal splice acceptor site of c-ets-1 exon alpha involved in the genesis of the E26 myb-ets sequence.
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PMID:Alternative splicing within the chicken c-ets-1 locus: implications for transduction within the E26 retrovirus of the c-ets proto-oncogene. 284 75

The stabilities of different mRNA species were analyzed in a reticulocyte lysate system under protein-synthesizing conditions. In all cases examined the relative mRNA degradation by reticulocyte ribonucleases as well as by the interferon-modulated (2'-5') (A)n-dependent endonuclease correlated with the extent of (U)nA sequences within the 3' non-coding region. The experimental data presented indicate that according to their stabilities at least three major mRNA groups may be identified: (a) (U)nA-poor mRNAs (e.g. globin) are essentially stable and are only slightly degraded by the (2'-5')(A)n-dependent endonuclease; (b) mRNA species with intermediate (U)nA levels (e.g. Ig alpha and Ig mu heavy-chain mRNAs) are partially degraded by general ribonuclease activity and further degraded by the (2'-5')(A)n-dependent endonuclease and (c) (U)nA-rich mRNA species (such as c-myc and non-skeletal actin mRNAs) are inherently unstable and are extremely sensitive to degradation by general ribonuclease activity. A survey of mRNA nucleotide sequences demonstrated that without exception (U)nA-rich stretches appeared more frequently within the 3' non-coding region than in the coding or 5' non-coding regions. A comparison of 3' non-coding region sequences from 92 different mRNAs revealed that transiently expressed mRNAs, such as the interleukins, nerve growth factor, epidermal growth factor receptor, c-myc, c-fos, c-myb and several other oncogenes as well as interferons alpha, beta and gamma were exceptionally (U)nA-rich. It is postulated that differential mRNA stability may be partly determined by the primary nucleotide sequence and in particular by (U)nA sequences within the 3' non-coding region. This may represent a novel post-transcriptional strategy employed by the cell to selectively retain or destroy discrete mRNA species.
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PMID:Differential mRNA stability to reticulocyte ribonucleases correlates with 3' non-coding (U)nA sequences. 335

Mouse c-myb gene transcripts in various cells of haemopoietic origin were analysed using S1 nuclease and RNase mapping techniques and by Northern blotting. It was found that the prevalent 3.8-kb c-myb mRNA present in thymocytes, T cell leukaemias, myelomonocytic leukaemias, erythroleukaemias and myeloid stem cells was initiated at several cap sites mapping within a region 97-244 bp upstream from the protein coding sequence. Utilization of additional cap sites mapping further upstream was also observed in certain cells, most notably thymocytes, and this gave rise to RNA species (4.3-5.6 kb) larger than the presumptive mRNA. In contrast, myeloma cell c-myb transcripts, which are much less abundant than those in more immature haemopoietic cells, were found to be initiated at a restricted set of cap sites mapping 244-277 bp upstream of the coding sequence. Hence, these data suggest that the abundance of the c-myb mRNA may be regulated by a process involving selective utilization of mRNA cap sites. Sites hypersensitive to DNase I were associated with mRNA cap sites in cells that expressed c-myb.
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PMID:Multiple c-myb transcript cap sites are variously utilized in cells of mouse haemopoietic origin. 360 90

The possible roles of certain oncogenes in the development of pituitary tumors has not been investigated. We have examined the expression of c-myc, c-fos, and c-myb in a number of human pituitary tumors by ribonuclease protection assays, as these oncogenes have been implicated to have roles in the pathogenesis of other human tumors (12, 13, 15, 16). In several tumors examined (9 of 30) c-myc was expressed at levels 4-9 times greater than the level detected in normal postmortem pituitary. Although a larger percentage of negative immunohistochemical-staining tumors overexpressed c-myc, c-myc over-expression was not limited to this group of tumors. c-Fos was overexpressed in 1 of 30 tumors examined at a level 5.8-fold higher than that detected in normal postmortem pituitary. This tumor stained positive for ACTH by immunohistochemistry and was considered highly aggressive, demonstrating invasion beyond the sella turcica; however, when other ACTH-staining and invasive pituitary tumors were examined, no abnormality in the expression of c-fos was detected. In 30 tumors, c-myb was expressed at approximately the same level as that detected in normal postmortem pituitary. We conclude that c-myc is overexpressed in a subgroup of pituitary tumors and that this overexpression occurs broadly among the different groups of immunohistochemical-staining tumors. c-Fos overexpression appears to be much less common in pituitary tumors and does not necessarily correlate with the ability of the tumor to become invasive. c-Myb does not appear to have a role in the pathogenesis of pituitary tumors.
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PMID:c-myc, c-fos, and c-myb gene expression in human pituitary adenomas. 802 38

The ABPL tumor cell lines represent a group of myeloid cell lines which contain an altered myb locus due to viral insertional mutagenesis within the third exon of c-myb. Immunoprecipitation analysis of the proteins produced in three ABPL lines revealed an interesting anomaly. Despite the invariant position of the virus integration event, the three ABPL tumor cell lines we examined (ABPL-1, ABPL-2 and ABPL-4) produced three different sized proteins. In this report, we examined the molecular basis for this protein size heterogeneity. Molecular cloning and sequence analysis of the cDNAs derived from the myb transcripts show that ABPL-1 tumor produces a tripartate mRNA containing sequences derived from the viral gag and env genes fused to the myb coding region. This results in the synthesis of a 74 kd protein. In the ABPL-2 tumor line, a gag-myb fusion protein is produced which is of 68 kd. In ABPL-4 cell line a gag-myb fusion protein is produced which contains an internal deletion of coding sequences derived from exons 13 and 14. This deletion results in the synthesis of a 59 kd protein in ABPL-4 tumor cell line. These observations were further confirmed by RNase protection assays which demonstrate the presence of aberrantly spliced mRNAs in ABPL-1 and ABPL-4 tumor cells but not in cells containing an undisrupted c-myb locus. In vitro translation and immuno-precipitation analysis of the cRNAs derived from the ABPL-1, ABPL-2 and ABPL-4 cDNAs show the synthesis of protein products that were identical to Myb proteins produced by these tumors in vivo. These results suggest that integration of Mo-MuLV within the c-myb locus not only results in deletions of the 5' end of the transcript but splicing aberrations within the encoded mRNA, which results in the synthesis of a heterogeneous array of proteins, not seen in normal hematopoietic cells.
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PMID:Murine myeloid leukemic cells with disrupted myb loci show splicing anomalies that account for heterogeneous sizes in myb proteins. 880 93

c-myb expression is an indicator of hemopoietic cell proliferation and its down-regulation occurs as an early event in cellular differentiation in vitro. We have previously demonstrated c-Myb protein expression in normal adult colon and tumor-derived colonic cell lines and have also shown that the proliferation of colon carcinoma cell lines is c-myb dependent. This study used the techniques of RNase protection and immunohistochemistry to define c-myb mRNA and protein expression in the normal adult mouse and mouse embryos, with special focus on the colon. These experiments revealed wide-spread c-myb mRNA expression in mouse embryos including nonhemopoietic tissues, and developmental time course studies revealed alterations in organ-specific c-myb mRNA expression. Immunohistochemical studies confirmed the embryonal expression of c-Myb in concordance with the mRNA data as well as c-Myb expression throughout the length of the adult mouse colonic crypt. In contrast, staining for the proliferating cell nuclear antigen was confined to the lower one third of the crypt. In addition, c-Myb staining extended beyond that of the proliferating cell nuclear antigen within the germinal centers of the spleen. These data suggest that c-myb: (a) has a role in the embryonic development of nonhemopoietic organs; (b) plays a specific role in the biology of the normal adult colonic crypt; and (c) expression is not inextricably linked to proliferation in vivo.
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PMID:Colonic expression of c-myb is initiated in utero and continues throughout adult life. 880 14