长链非编码RNA SNHG1与剪接因子相互作用影响红细胞分化

doi:10.16352/j.issn.1001-6325.2026.05.0651

基础医学与临床 ›› 2026, Vol. 46 ›› Issue (5): 651-657.doi: 10.16352/j.issn.1001-6325.2026.05.0651

长链非编码RNA SNHG1与剪接因子相互作用影响红细胞分化

沈欣妍, 郭嘉, 马艳妮, 余佳, 刘思琪^*

中国医学科学院北京协和医学院基础医学研究所生物化学与分子生物学系重大疾病共性机制研究全国重点实验室,北京 100005

收稿日期:2026-01-06 修回日期:2026-03-24 出版日期:2026-05-05 发布日期:2026-04-28
通讯作者: ^*liusiqi0215@163.com
基金资助:
国家自然科学基金(32470847)

Long non-coding RNA SNHG1 interacting with splicing factors influences erythroid differentiation

SHEN Xinyan, GUO Jia, MA Yanni, YU Jia, LIU Siqi^*

State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China

Received:2026-01-06 Revised:2026-03-24 Online:2026-05-05 Published:2026-04-28
Contact: ^*liusiqi0215@163.com

摘要/Abstract

摘要： 目的探究长链非编码RNA(lncRNA)小核仁RNA宿主基因1(SNHG1)在红系分化中的功能及分子机制。方法在人脐带血来源的CD34⁺造血干祖细胞的红系诱导分化过程中,抑制SNHG1表达。流式细胞测量术检测红系分化标志物CD71/CD235a;RT-qPCR分析珠蛋白mRNA的表达水平;细胞核质分离与RNA荧光原位杂交技术(RNA-FISH)定位SNHG1;RNA pull-down与RNA免疫共沉淀(RIP)鉴定SNHG1的相互作用蛋白质。结果抑制SNHG1表达后,CD71/CD235a双阳性红系祖细胞比例明显减少(P＜0.001),珠蛋白基因表达水平显著下降(P＜0.01)。SNHG1主要定位在细胞核,并可与SFPQ、NONO等多个剪接调控蛋白质相互作用。结论 SNHG1可能通过招募SFPQ、NONO等剪接相关蛋白质,参与调控RNA剪接等加工过程,从而影响红系分化。

关键词: 长链非编码RNA(lncRNA), 红系分化, RNA剪接

Abstract: Objective To investigate the function and molecular mechanism of long non-coding RNA (lncRNA) small nucleolar RNA host gene 1(SNHG1) in erythroid differentiation. Methods During erythroid differentiation of CD34⁺ hematopoietic stem/progenitor cells derived from human umbilical cord blood, expression of SNHG1 was suppressed. Erythroid differentiation was assessed by flow cytometry with surface markers CD71 and CD235a, while the mRNA expression of globin genes was measured by reverse transcription quantitative PCR (RT-qPCR). Nuclear-cytoplasm fractionation and RNA fluorescence in situ hybridization (RNA-FISH) were applied to determine the sub-cellular localization of SNHG1. RNA pull-down and RNA immunoprecipitation (RIP) assays were applied to identify SNHG1-interacting proteins. Results Suppression of SNHG1 significantly decreased the proportion of CD71⁺/CD235a⁺ erythroid progenitor cells(P＜0.001) and reduced the expression of globingene (P＜0.01).SNHG1 was found to be predominantly localized in the nucleus and interacted with multiple splicing regulators, including SFPQ and NONO. Conclusions SNHG1 may affect erythroid differentiation by recruiting splicing-related proteins such as SFPQ and NONO and thereby regulating RNA splicing and processing.

Key words: long non-coding RNA (lncRNA), erythroid differentiation, RNA splicing

中图分类号:

沈欣妍, 郭嘉, 马艳妮, 余佳, 刘思琪. 长链非编码RNA SNHG1与剪接因子相互作用影响红细胞分化[J]. 基础医学与临床, 2026, 46(5): 651-657.

SHEN Xinyan, GUO Jia, MA Yanni, YU Jia, LIU Siqi. Long non-coding RNA SNHG1 interacting with splicing factors influences erythroid differentiation[J]. Basic & Clinical Medicine, 2026, 46(5): 651-657.

参考文献 13

[1]	Hattangadi SM, Wong P, Zhang L, et al. From stem cell to red cell: regulation of erythropoiesis at multiple levels by multiple proteins, RNAs, and chromatin modifications[J]. Blood, 2011, 118:6258-6268.
[2]	Alvarez-Dominguez JR, Hu W, Yuan B, et al. Global discovery of erythroid long noncoding RNAs reveals novel regulators of red cell maturation[J]. Blood, 2014, 123:570-581.
[3]	Paralkar VR, Mishra T, Luan J, et al. Lineage and species-specific long noncoding RNAs during erythro-megakaryocytic development[J]. Blood, 2014, 123:1927-1937.
[4]	Hu W, Yuan B, Flygare J, et al. Long noncoding RNA-mediated anti-apoptotic activity in murine erythroid terminal differentiation[J]. Genes Dev, 2011, 25:2573-2578.
[5]	Clemson CM, Hutchinson JN, Sara SA, et al. NEAT1 RNA is essential for the structure of paraspeckles[J]. Mol Cell, 2009, 33:717-726.
[6]	Imamura K, Imamachi N, Akizuki G, et al. Long noncoding RNA NEAT1-dependent SFPQ relocation mediates gene regulation upon stimuli[J]. Mol Cell, 2014, 53:393-406.
[7]	Pimentel H, Parra M, Gee SL, et al. A dynamic alternative splicing program regulates gene expression during terminal erythropoiesis[J]. Nucleic Acids Res, 2014, 42:4031-4042.
[8]	Knott GJ, Bond CS, Fox AH. The DBHS proteins SFPQ, NONO and PSPC1: a multipurpose molecular scaffold[J]. Nucleic Acids Res, 2016, 44:3989-4004.
[9]	Jaafar L, Li Z, Li S, et al. SFPQ NONO and XLF function separately and together to promote DNA double-strand break repair via canonical nonhomologous end joining[J]. Nucleic Acids Res, 2017, 45:1848-1859.
[10]	Thin KZ, Tu JC, Raveendran S. Long non-coding SNHG1 in cancer[J]. Clin Chim Acta, 2019, 494:38-47.
[11]	Azad P, Zhou D, Tu H-C, et al. Long noncoding RNA HIKER regulates erythropoiesis in Monge′s disease via CSNK2B[J]. J Clin Invest, 2023, 133:e165831. doi: 10.1172/JCI165831.
[12]	Rasmussen T, Küspert J, Schönemann L, et al. The gene-regulating proteins NONO and SFPQ assemble into ordered filaments[J]. Commun Biol, 2025, 9:117.doi:10.1038/s42003-025-09396-8.
[13]	Li Y, Wang D, Wang H, et al. A splicing factor switch controls hematopoietic lineage specification of pluripotent stem cells[J]. EMBO Rep, 2021, 22:e50535. doi: 10.15252/embr.202050535.

长链非编码RNA SNHG1与剪接因子相互作用影响红细胞分化

Long non-coding RNA SNHG1 interacting with splicing factors influences erythroid differentiation

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