Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA112265 | ENA |
REPOSITORIES: ENA
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Project description:Many classes of noncoding RNAs (ncRNAs) are known to be involved in gene expression regulation; however, long intronic ncRNAs have received little attention. In previous works, our group has provided evidence that intronic regions, transcribed from 80% of all RefSeq gene loci, are key sources of potentially regulatory ncRNAs. Intronic transcripts were shown to be correlated to the degree of prostate cancer differentiation, regulated by physiological stimuli, and highly expressed in genomic loci related to transcriptional regulation. In the present work we aimed at functional characterization of KLHL29 intronic transcript, one of the most highly expressed in human tissues. Although the protein-coding KLHL29 transcripts are still poorly studied, genes from this family are involved in a wide variety of biological processes, including cell cycle regulation mechanisms. We have observed that the long intronic ncRNA is predominantly transcribed from the opposite strand at the KLHL29 locus, and that the ncRNA overexpression does not affect the levels of protein-coding mRNAs from the same locus. Intriguingly, we found 2,002 genes with significant (q< 5.3%) differential expression between HEK293 cells overexpressing KLHL29 sense (S) or antisense (AS) intronic transcript. Within these genes, GO categories such as ‘Regulation of cell cycle’ and ‘Transcription’ were significantly enriched. Furthermore, human tumorigenic cell lines overexpressing KLHL29 AS intronic transcript showed increased proliferation rates in vitro and increased tumorigenic capacity in nude mice. In conclusion, we suggest that KLHL29 long intronic ncRNA controls the cell cycle mechanisms, probably through a fine-tuning regulation of gene expression.
2009-07-30 | GSE14681 | GEO
Project description:Approximately half of all microRNAs reside within intronic regions and are often co-transcribed with their host genes. However, most studies on intronic microRNAs focus on individual microRNAs, and conversely most studies on protein-coding and non-coding genes frequently ignore any intron-derived microRNAs. We hypothesize that the individual components of such multi-genic loci may play cooperative or competing roles in driving disease progression, and that examining the combinatorial effect of these components would uncover deeper insights into their functional importance. To address this, we perform systematic analyses of intronic microRNA:host loci in colon cancer. We observe that the FTX locus, comprising of a long non-coding RNA FTX and multiple intronic microRNAs, is highly upregulated in cancer and demonstrate that cooperativity within this multi-component locus promotes cancer growth. In addition, we show that FTX interacts with DHX9 and DICER and delineate its novel roles in regulating A-to-I RNA editing and microRNA expression. These results show for the first time that a long non-coding RNA can regulate A-to-I RNA editing, further expanding the functional repertoire of long non-coding RNAs. We further demonstrate the inhibitory effects of intronic miR-374b and -545 on the tumor suppressors PTEN and RIG-I to enhance the proto-oncogenic PI3K-AKT signaling. Finally, we show that intronic miR-421 may exert an autoregulatory effect on miR-374b and -545. Taken together, our data unveil the intricate interplay between intronic microRNAs and their host transcripts in the modulation of key signaling pathways and disease progression, adding new perspectives to the functional landscape of multi-genic loci.
2021-01-05 | PXD021823 | Pride
Project description:Many classes of noncoding RNAs (ncRNAs) are known to be involved in gene expression regulation; however, long intronic ncRNAs have received little attention. In previous works, our group has provided evidence that intronic regions, transcribed from 80% of all RefSeq gene loci, are key sources of potentially regulatory ncRNAs. Intronic transcripts were shown to be correlated to the degree of prostate cancer differentiation, regulated by physiological stimuli, and highly expressed in genomic loci related to transcriptional regulation. In the present work we aimed at functional characterization of KLHL29 intronic transcript, one of the most highly expressed in human tissues. Although the protein-coding KLHL29 transcripts are still poorly studied, genes from this family are involved in a wide variety of biological processes, including cell cycle regulation mechanisms. We have observed that the long intronic ncRNA is predominantly transcribed from the opposite strand at the KLHL29 locus, and that the ncRNA overexpression does not affect the levels of protein-coding mRNAs from the same locus. Intriguingly, we found 2,002 genes with significant (q< 5.3%) differential expression between HEK293 cells overexpressing KLHL29 sense (S) or antisense (AS) intronic transcript. Within these genes, GO categories such as ‘Regulation of cell cycle’ and ‘Transcription’ were significantly enriched. Furthermore, human tumorigenic cell lines overexpressing KLHL29 AS intronic transcript showed increased proliferation rates in vitro and increased tumorigenic capacity in nude mice. In conclusion, we suggest that KLHL29 long intronic ncRNA controls the cell cycle mechanisms, probably through a fine-tuning regulation of gene expression. Genes were defined as expressed when their intensity signals were above the average negative control value plus three standard deviations; a set of 153 negative controls (Agilent Technologies) was present on the array. Only genes that were detected as expressed in all four replicates of the same HEK293 transfection (or not expressed in the four replicates) were used in further analysis. The intensity values between experiments were normalized by the 40% trimmed mean intensity. For each transfection, one entire replicate experiment was excluded from the analyses, based on evaluating the coefficient of variance among the samples (for S KLHL29 intronic transcript, exclusion of the outlier replicate decreased the coefficient of variance from 0.21-0.24 (obtained by excluding any other replicate) to 0.19; for AS transcript, the coefficient of variance decreased from 0.17-0.18 to 0.12). Differentially expressed genes were identified using three transfection replicates for each construction, employing the Significance Analysis of Microarrays (SAM) tool (Tusher et al., 2001) with the following parameters: two-class response, 100 permutations and K-Nearest Neighbors Imputer. We applied 5.4 or 10.3% FDR (False Discovery Rate) cutoffs, as described in the results. A fold-change filter (1.4-fold cutoff) was applied after identification of significant differentially expressed genes.
2009-07-29 | E-GEOD-14681 | biostudies-arrayexpress
Project description:EPR is a long non-coding RNA (lncRNA) that controls cell proliferation in mammary gland cells by regulating gene transcription. Here, we report on Mettl7a1 as a direct target of EPR. We show that EPR induces Mettl7a1 transcription by rewiring three-dimensional chromatin interactions at the Mettl7a1 locus. Our data indicate that METTL7A1 contributes to EPR-dependent inhibition of TGF-β signaling. METTL7A1 is absent in tumorigenic murine mammary gland cells and its human ortholog (METTL7A) is downregulated in breast cancers. Importantly, re-expression of METTL7A1 in 4T1 tumorigenic cells attenuates their transformation potential, with the putative methyltransferase activity of METTL7A1 being dispensable for its biological functions. We found that METTL7A1 localizes in the cytoplasm whereby it interacts with factors implicated in the early steps of mRNA translation, associates with ribosomes, and affects the levels of target proteins without altering mRNA abundance. Overall, our data indicates that METTL7A1 —a transcriptional target of EPR— modulates translation of select transcripts.
2022-08-12 | PXD034398 | Pride
Project description:BACKGROUND: Transcription of large numbers of non-coding RNAs originating from intronic regions of human genes has been recently reported, but mechanisms governing their biosynthesis and biological functions are largely unknown. In this work, we evaluated the existence of a common mechanism of transcription regulation shared by protein-coding mRNAs and intronic RNAs by measuring the effect of androgen on the transcriptional profile of a prostate cancer cell line. RESULTS: Using a custom-built cDNA microarray enriched in intronic transcribed sequences, we found 39 intronic non-coding RNAs for which levels were significantly regulated by androgen exposure. Orientation-specific reverse transcription-PCR indicated that 10 of the 13 were transcribed in the antisense direction. These transcripts are long (0.5-5 kb), unspliced and apparently do not code for proteins. Interestingly, we found that the relative levels of androgen-regulated intronic transcripts could be correlated with the levels of the corresponding protein-coding gene (asGAS6 and asDNAJC3) or with the alternative usage of exons (asKDELR2 and asITGA6) in the corresponding protein-coding transcripts. Binding of the androgen receptor to a putative regulatory region upstream from asMYO5A, an androgen-regulated antisense intronic transcript, was confirmed by chromatin immunoprecipitation. CONCLUSIONS: Altogether, these results indicate that at least a fraction of naturally transcribed intronic non-coding RNAs may be regulated by common physiological signals such as hormones, and further corroborate the notion that the intronic complement of the transcriptome play functional roles in the human gene-expression program. Keywords: Time course study – effect of androgen on gene expression
2007-01-01 | GSE5345 | GEO
Project description:Long non-coding RNA expression in Human tissues and cell lines
| PRJNA150189 | ENA
Project description:EPR is a long non-coding RNA (lncRNA) that controls cell proliferation in mammary gland cells by regulating gene transcription and, here, we report on Mettl7a1 as a target of EPR. We show that the lncRNA induces Mettl7a1 transcription by remodeling the 3-dimensional chromatin structure at the Mettl7a1 locus. Our data indicate that METTL7A1 participates in the EPR-dependent pathway that antagonizes TGF-β signaling. METTL7A1 is absent in tumorigenic murine mammary gland cells and its human ortholog (METT7A) is downregulated in breast cancers. Importantly, expression of METTL7A1 in 4T1 tumorigenic cells reduces their transformation potential, and the putative methyltransferase activity of METTL7A1 appears dispensable for its biological functions. METTL7A1 is a cytoplasmic protein and, from a mechanistic perspective, interacts with factors implicated in the early steps of mRNA translation, associates with ribosomes, and affects the levels of select proteins without substantial changes in mRNA abundance. Our data suggest the possibility that METTL7A1 conveys the transcriptional regulation operated by EPR into specific changes of mRNA translation.
2022-05-28 | GSE195822 | GEO
Project description:EPR is a long non-coding RNA (lncRNA) that controls cell proliferation in mammary gland cells by regulating gene transcription and, here, we report on Mettl7a1 as a target of EPR. We show that the lncRNA induces Mettl7a1 transcription by remodeling the 3-dimensional chromatin structure at the Mettl7a1 locus. Our data indicate that METTL7A1 participates in the EPR-dependent pathway that antagonizes TGF-β signaling. METTL7A1 is absent in tumorigenic murine mammary gland cells and its human ortholog (METT7A) is downregulated in breast cancers. Importantly, expression of METTL7A1 in 4T1 tumorigenic cells reduces their transformation potential, and the putative methyltransferase activity of METTL7A1 appears dispensable for its biological functions. METTL7A1 is a cytoplasmic protein and, from a mechanistic perspective, interacts with factors implicated in the early steps of mRNA translation, associates with ribosomes, and affects the levels of select proteins without substantial changes in mRNA abundance. Our data suggest the possibility that METTL7A1 conveys the transcriptional regulation operated by EPR into specific changes of mRNA translation.
2022-05-28 | GSE195821 | GEO
Project description:EPR is a long non-coding RNA (lncRNA) that controls cell proliferation in mammary gland cells by regulating gene transcription and, here, we report on Mettl7a1 as a target of EPR. We show that the lncRNA induces Mettl7a1 transcription by remodeling the 3-dimensional chromatin structure at the Mettl7a1 locus. Our data indicate that METTL7A1 participates in the EPR-dependent pathway that antagonizes TGF-β signaling. METTL7A1 is absent in tumorigenic murine mammary gland cells and its human ortholog (METT7A) is downregulated in breast cancers. Importantly, expression of METTL7A1 in 4T1 tumorigenic cells reduces their transformation potential, and the putative methyltransferase activity of METTL7A1 appears dispensable for its biological functions. METTL7A1 is a cytoplasmic protein and, from a mechanistic perspective, interacts with factors implicated in the early steps of mRNA translation, associates with ribosomes, and affects the levels of select proteins without substantial changes in mRNA abundance. Our data suggest the possibility that METTL7A1 conveys the transcriptional regulation operated by EPR into specific changes of mRNA translation.
2022-05-28 | GSE195819 | GEO