論文 - 詳細
| RRC ID | 89464 |
|---|---|
| 著者 | Rahaman M, Bhattacharya S, Mukherjee M, Bhowmick C, Shukla PC, Dolai TK, Chakravorty N. |
| タイトル | UCA1 lncRNA regulates γ-globin expression by modulating the miR-148b/BCL11A axis. |
| ジャーナル | Life Sci Alliance |
| Abstract |
The switch from fetal to adult hemoglobin is tightly regulated during erythropoiesis, and its dysregulation can contribute to β-hemoglobinopathies. Although transcriptional repression of γ-globin by BCL11A is well established, the posttranscriptional mechanisms that sustain BCL11A expression in adult erythroid cells remain incompletely understood. Here, we report that the long noncoding RNA UCA1/miR-148b-mediated regulatory axis is critical for globin gene switching. We identified miR-148b as a direct posttranscriptional regulator of BCL11A. lncRNA UCA1, which is abundantly expressed in adult erythroid cells, functions as a molecular decoy for miR-148b, thereby attenuating miR-148b-mediated repression of BCL11A. Depletion of UCA1 increases miR-148b availability and reduces BCL11A expression, which can lead to robust induction of γ-globin. Conversely, the ectopic expression of UCA1 restores BCL11A levels by antagonizing miR-148b, thereby promoting γ-globin silencing in adult erythroid cells. Mechanistically, UCA1 orchestrates a posttranscriptional regulatory axis that reinforces γ-globin silencing by stabilizing BCL11A levels in adult erythroid cells. Taken together, our studies uncover a previously unrecognized lncRNA-mediated mechanism that integrates miRNA activity with transcriptional control to fine-tune hemoglobin switching during adult erythropoiesis. |
| 巻・号 | 9(9) |
| 公開日 | 2026-9-1 |
| DOI | 10.26508/lsa.202603620 |
| PII | 9/9/e202603620 |
| PMID | 42373543 |
| PMC | PMC13315483 |
| MeSH | Animals Carrier Proteins* / genetics Carrier Proteins* / metabolism Erythroid Cells / metabolism Erythropoiesis / genetics Gene Expression Regulation Humans MicroRNAs* / genetics MicroRNAs* / metabolism Nuclear Proteins* / genetics Nuclear Proteins* / metabolism RNA, Long Noncoding* / genetics RNA, Long Noncoding* / metabolism Repressor Proteins* / genetics Repressor Proteins* / metabolism gamma-Globins* / genetics gamma-Globins* / metabolism |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 8 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.7 |
| リソース情報 | |
| ヒト・動物細胞 | HUDEP-2(RCB4557) |