人类基因组测序计划发现多于98%的转录基因组序列为非编码RNA(ncRNA)。这些ncRNA包括人们所熟知的housekeepingncRNA(如tRNAs, rRNAs和snRNAs等)、小RNA(如miRNAs和piRNAs等)，以及上万条长非编码RNA(lncRNA，>200nt)。最近几年来的研究表明lncRNAs广泛参与一系列细胞的重要功能调控，包括细胞核亚结构的形成、基因表达的遗传与表观遗传调控等。

　　我们实验室主要研究哺乳动物细胞中lncRNAs的功能调控，包括新类型lncRNA分子的发掘、其加工成熟机制、以及它们在转录、染色体、细胞核亚结构和干细胞干性维持等方面的调控功能研究。未来五年，我们主要研究以下内容：

　　1、通过转录组测序和计算生物学手段结合的方法，发掘和鉴定人类基因组中的新类型lncRNA分子

　　2、利用分子生物学、细胞生物学和生物化学的手段，研究新lncRNA分子在基因表达调控中的作用机制

　　3、采用基因组编辑和活细胞成像等技术手段，研究lncRNA在细胞核亚结构和染色体维持和调控过程中的功能

　　4、以hESCs的多功能潜能性维持和分化为模型，研究lncRNA对人源胚胎干细胞的命运决定的调控

　　研究成果将能够丰富我们对lncRNAs功能和机制的认识，也为hESCs的多功能性维持和命运改变提供一个全新水平的调控。

1. Shan L^#, Xu G^#, Yao RW, Luan PF, Huang YK, Zhang PH, Pan YH, Zhang L, Gao X, Li Y, Cao SM, Gao SX, Yang ZH, Li SQ, Yang LZ, Wang Y, Wong CC, Yu L, Li JS, Yang L and Chen LL*. 2023. Nucleolar URB1 ensures 3' ETS rRNA removal to prevent exosome-surveillance. Nature, 615(7952):526-534.
2. Chen LL*, Bindereif A, Bozzoni I, Chang HY, Matera GA, Gorospe Y, Hansen TB, Kjems J, Ma XK, Pek JW, Rajewsky N, Salzman J, Wilusz JE*, Yang L* and Zhao F. 2023. A guide to naming eukaryotic circular RNAs. Nat Cell Biol, 25(1):1-5.
3. Mattick JS*, Amaral PP, Carninci P, Carpenter S, Chang HY, Chen LL, Chen R, Dean C, Dinger ME, Fitzgerald KA, Gingeras TR, Guttman M, Hirose T, Huarte M, Johnson R, Kanduri C, Kapranov P, Lawrence JB, Lee JT, Mendell JT, Mercer TR, Moore KJ, Nakagawa S, Rinn JL, Spector DL, Ulitsky I, Wan Y, Wilusz JE and Wu M. 2023. Long non-coding RNAs: definitions, functions, challenges and recommendations. Nat Rev Mol Cell Biol, 24(6):430-447.
4. Huang YK, Gao BQ, Meng Q, Yang LZ, Ma XK, Wu H, Pan YH, Yang L, Li D and Chen LL*. 2023. CRISPR-dCas13-tracing reveals transcriptional memory and limited mRNP export in developing embryos. Genome Biol, 24(1):15.
5. Chen LL*. 2022. Towards higher-resolution and in vivo understanding of lncRNA biogenesis and function. Nat Methods, 19(10):1152-1155.
6. Wu H and Chen LL*. 2022. 7S RNA is surveilling mitochondrial DNA transcription. Life Metab, 1(1):8-9.
7. Yang LZ^#, Gao BQ^#, Huang YK, Wang Y, Yang L and Chen LL*. 2022. Multi-color RNA imaging with CRISPR-Cas13b systems in living cells. Cell Insight, 1(4):100044.
8. Li SQ^#, Wu H^# and Chen LL*. 2022. Screening circular RNAs with functional potential using the RfxCas13d/BSJ-gRNA system. Nat Protoc, 17(9):2085-2107.
9. Yang L*, Wilusz JE* and Chen LL*. 2022. Biogenesis and regulatory roles of circular RNAs. Annu Rev Cell Dev Biol, 38:263-289.
10. Liu CX and Chen LL*. 2022. Circular RNAs: characterization, cellular roles, and applications. Cell, 185(12):2016-2034.
11. Liu JQ*, Yang LZ and Chen LL*. 2022. Understanding lncRNA-protein assemblies with imaging and single-molecule approaches. Curr Opin Genet Dev, 72:128-137.
12. Liu CX, Guo SK, Nan F, Xu YF, Yang L and Chen LL*. 2022. RNA circles with minimized immunogenicity as potent PKR inhibitors. Mol Cell, 82(2):420-434.
13. Liu CX and Chen LL*. 2021. Expanded regulation of circular RNA translation. Mol Cell, 81(20):4111-4113.
14. Wu M, Yang LZ and Chen LL*. 2021. Long noncoding RNA and protein abundance in lncRNPs. RNA, 27(12):1427-1440. (Mid-Career Research Awardee Review).
15. Li X, Zhang JL, Lei YN, Liu XQ, Xue W, Zhang Y, Nan F, Gao X, Zhang J, Wei J, Yang L and Chen LL*. 2021. Linking circular intronic RNA degradation and function in transcription by RNase H1. Sci China Life Sci, 64(11):1795-1809. (Cover article).
16. Wu M^#, Xu G^#, Han C^#, Luan PF, Xing YH, Nan F, Yang LZ, Huang YK, Yang ZH, Shan L, Yang L, Liu JQ* and Chen LL*. 2021. lncRNA SLERT controls phase separation of FC/DFCs to facilitate Pol I transcription. Science, 373(6554):547-555. (Preview by Yamazaki T and Hirose T, Science, 2021, 373:486-487; Research highlights by Nat Cell Biol, 2021, 23:927).
17. Xu G, Wu M and Chen LL*. 2021. LETN and NPM1 tango in human nucleoli. Cell Res, 31(6):609-610.
18. Wang XW, Liu CX, Chen LL* and Qiangfeng Cliff Zhang*. 2021. RNA structure probing uncovers RNA structure-dependent biological functions. Nat Chem Biol, 17(7):755-766.
19. Yao RW, Luan PF and Chen LL*. 2021. An optimized fixation method containing glyoxal and paraformaldehyde for imaging nuclear bodies. RNA, 27(6):725-733.
20. Statello L^#, Guo CJ^#, Chen LL* and Huarte M*. 2021. Gene regulation by long noncoding RNAs and its biological functions. Nat Rev Mol Cell Biol, 22(2):96-118.
21. Li SQ^#, Li X^#, Xue W^#, Zhang L^#, Yang LZ, Cao SM, Lei YN, Liu CX, Guo SK, Shan L, Wu M, Tao X, Zhang JL, Gao X, Zhang J, Wei J, Li JS^*, Yang L* and Chen LL*. 2021. Screening for functional circular RNAs using the CRISPR-Cas13 system. Nat Methods, 18(1):51-59. (The Author Profile of this Month by Vivian Marx, Nat Methods, 2021, 18:3; Research highlights by Nat Rev Genet, 2021, 22(2):68).
22. Guo CJ, Xu G and Chen LL*. 2020. Mechanisms of Long Noncoding RNA Nuclear Retention. Trends Biochem Sci, 45(11):947-960.
23. Wang Y and Chen LL*. 2020. Organization and function of paraspeckles. Essays Biochem, 64(6):875-882.
24. Chen LL*. 2020. The expanding regulatory mechanisms and cellular functions of circular RNAs. Nat Rev Mol Cell Biol, 21(8):475-490.
25. Guo CJ^#, Ma XK^#, Xing YH, Zheng CC, Shan L, Xu YF, Zhang J, Wang SH, Wang YM, Carmichael GG, Yang L and Chen LL*. 2020. Distinct processing of lncRNAs contributes to non-conserved functions in stem cells. Cell, 181(3):621-636. (Preview by Sharma H and Carninci P, Cell, 2020, 181(3):512-514).
26. Wang Y^#*, Yang LZ^# and Chen LL*. 2020. Protocol for dynamic imaging of RNA in living cells by CRISPR-Cas13 system. Star Protocols, Jun 3; 1(1):100037.
27. Yao RW, Liu CX and Chen LL*. 2020. Linking RNA processing and function. Cold Spring Harb Symp Quant Biol, 84:67-82.
28. Yang LZ^#, Wang Y^#, Li SQ, Yao RW, Luan PF, Wu H, Carmichael GG and Chen LL*. 2019. Dynamic imaging of RNA in living cells by CRISPR-Cas13 system. Mol Cell, 76(6):981-997. (F1000 Prime recommendation and Spotlighted by Davis BJ and O’Connell MR, Mol Cell, 2020, 77:207-209).
29. Yao RW^#, Xu G^#, Wang Y, Shan L, Luan PF, Wang Y, Wu M, Yang LZ, Xing YH, Yang L and Chen LL*. 2019. Nascent pre-rRNA sorting via phase separation drives the assembly of dense fibrillar components in the human nucleolus. Mol Cell, 76(5):767-783. (Featured article and Issue highlights; Preview by Lafontaine DL, Mol Cell, 2019, 76(5): 694-696; Research Highlights by Nat Chem Biol, 2019, 15:1029).
30. Liu CX^#, Li X^#, Nan F^#, Jiang S, Gao X, Guo SK, Xue W, Cui YG, Dong KG, Ding HH, Qu B, Shen N^*, Yang L^*and Chen LL*. 2019. Structure and degradation of circular RNAs regulate PKR activation in innate immunity. Cell, 177(4):865-880. (Preview by Wilusz JE, Cell, 2019, 177:797-799; Research highlights by Nat Rev Immunol, 2019, 19:351; Nat Rev Mol Cell Biol, 2019, 20:387; Science, 2019, 364:847; Cell Bioscience, 2019, 9:43-45; Bull Chin Acad Sci, 2019, 33:91-95; Recommended by F1000 Prime; News reports by Science News Magazine, LUPUS NEWS, Technologytimes, Medical Xpress).
31. Yao RW^#, Wang Y^# and Chen LL*. 2019. Cellular functions of long noncoding RNAs. Nat Cell Biol, 21(5):542-551. (Editorial by Nat Cell Biol, 2019, 21(5):535).
32. Wang Y^#, Hu SB^#, Wang MR^#, Yao RW, Wu D, Yang L and Chen LL*. 2018. Genome-wide screening of NEAT1 regulators reveals cross-regulation between paraspeckles and mitochondria. Nat Cell Biol, 20(10):1145-1158. (News and Views by Fox AH, Nat Cell Biol, 2018, 20: 1108-1109).
33. Xing YH and Chen LL*. 2018. Processing and roles of snoRNA-ended long noncoding RNAs. Crit Rev Biochem Mol Biol, 53(6):596-606.
34. Li X, Yang L* and Chen LL*. 2018. The biogenesis, functions and challenges of circular RNAs. Mol Cell, 71(3):428-442.
35. Xiang JF^#, Yang Q^#, Liu CX^#, Wu M, Chen LL* and Yang L*. 2018. N⁶-methyladenosines modulate A-to-I RNA editing. Mol Cell, 69(1):126-135.
36. Li X^#, Liu CX^#, Xue W^#, Zhang Y, Jiang S, Yin QF, Wei J, Yao RW, Yang L* and Chen LL*. 2017. Coordinated circRNA biogenesis and function with NF90/NF110 in viral infection. Mol Cell, 67(2):214-227. (Free featured article; Highlighted by Editor’s Note and Meet the Author; Preview by Cadena CY and Hur S, Mol Cell, 2017, 67:163-164).
37. Xing YH^#, Yao RW^#, Zhang Y^#, Guo CJ, Jiang S, Xu G, Dong R, Yang L and Chen LL*. 2017. SLERT regulates DDX21-rings associated with Pol I transcription. Cell, 169(4):664-678. (Research highlights by Bull Chin Acad Sci, 2017, 31:152-155).
38. Yang L* and Chen LL*. 2017. Enhancing the RNA engineering toolkit. Science, 358(6366):996-997.
39. Wu H, Yang L* and Chen LL*. 2017. The Diversity of Long Noncoding RNAs and Their Generation. Trends Genet, 33(8):540-552.
40. Chen LL* and Yang L*. 2017. AlUternative regulation for gene expression. Trends Cell Biol, 27(7):480-490.
41. Dong R^#, Ma XK^#, Chen LL* and Yang L*. 2017. Increased complexity of circRNA expression during species evolution. RNA Biol, 14(8):1064-1074.
42. Wu H^#, Yin QF^#, Luo Z^#, Yao RW, Zheng CC, Zhang J, Xiang JF, Yang L and Chen LL*. 2016. Unusual processing generates SPA lncRNAs that sequester multiple RNA binding proteins. Mol Cell, 64(3):534-548. (Cover story and Issue highlights; Preview by Li RH and Fox AH, Mol Cell, 2016, 64:435-437).
43. Chen LL*. 2016. The biogenesis and emerging roles of circular RNAs. Nat Rev Mol Cell Biol, 17(4):205-211. (Cover article).
44. Zhang XO^#, Dong R^#, Zhang Y^#, Zhang JL, Luo Z, Zhang J, Chen LL*and Yang L*. 2016. Diverse alternative back-splicing and alternative splicing landscape of circular RNAs. Genome Res, 26(9):1277-1287.
45. Zhang Y^#, Xue W^#, Li X, Zhang J, Zhang JL, Yang L* and Chen LL*. 2016. The biogenesis of nascent circular RNAs. Cell Rep, 15(3):611-624.
46. Chen LL*. 2016. Linking long noncoding RNA localization and function. Trends Biochem Sci, 41(9):761-772. (Series: Fresh Perspectives from Emerging Experts).
47. Hu SB, Yao RW and Chen LL*. 2016. Shedding light on paraspeckle structure by super-resolution microscopy. J Cell Biol, 214(7):789-791.
48. Hu SB, Xiang JF, Li X, Xu Y, Xue W, Huang M, Wong CC, Sagum CA, Bedford MT, Yang L, Cheng D* and Chen LL*. 2015. Protein arginine methyltransferase CARM1 attenuates the paraspeckle-mediated nuclear retention of mRNAs containing IRAlus. Genes Dev, 29(6):630-645. (Perspectives by Elbarbary RA and Maquat LE, Genes Dev, 2015, 29:687-689; Research highlights by Bull Chin Acad Sci, 2015, 29:108).
49. Xing YH^#, Bai ZQ^#, Liu CX, Hu SB, Ruan MH and Chen LL*. 2016. Research progress of long noncoding RNA in China. IUBMB Life, 68(11):887-893.
50. Chen T^#, Xiang JF^#, Zhu S^#, Chen S, Yin QF, Zhang XO, Zhang J, Feng H, Dong R, Li XJ, Yang L* and Chen LL*. 2015. ADAR1 is required for differentiation and neural induction by regulating microRNA processing in a catalytically independent manner. Cell Res, 25(4):459-476. (Highlighted by ESC& iPSC NEWS).
51. Yin QF^#, Hu SB^#, Xu YF, Yang L, Carmichael GG and Chen LL*. 2015. SnoVectors for nucelar expression of RNA. Nucleic Acids Res, 43(1):e5.
52. Chen LL* and Yang L*. 2015. Regulation of circRNA biogenesis. RNA Biol, 12(4):381-388.
53. Xiang JF, Yang L and Chen LL*. 2015. The long noncoding RNA regulation at the MYC locus. Curr Opin Genet Dev, 33:41-48.
54. Chen LL* and Yang L*. 2015. Gear up in circles. Mol Cell, 58(5):715-717.
55. Zhang XO^#, Wang HB^#, Zhang Y, Lu X, Chen LL* and Yang L*. 2014. Complementary sequence-mediated exon circularization. Cell, 159(1):134-147. (Featured article; Preview by Vicens Q and Westhof E, Cell, 2014,159:13-14; Research highlights by Nat Rev Genetics, 2014, 15:717 and Bull Chin Acad Sci, 2014, 28:282-284; F1000 Prime recommendation).
56. Xiang JF, Yin QF, Chen T, Zhang Y, Zhang XO, Wang HB, Ge JH, Lu XH, Yang L and Chen LL*. 2014. Human colorectal cancer-specific CCAT1-L lncRNA regulates long-range chromatin interactions in the MYC locus. Cell Res, 24(5):513-531. (Cover article; Research highlights by Younger ST and Rinn JL. Cell Res, 2014, 24:643-644; by Nature.com, Global Medical Discovery and National Science Review, 2015, 2:7-8).
57. Yang L* and Chen LL*. 2014. Microexons go big. Cell, 159(7):1488-1489.
58. Zhang Y, Yang L and Chen LL*. 2014. Life without A tail: new formats of long noncoding RNAs. Int J Biochem Cell Biol, 54:338-349.
59. Zhang XO^#, Yin QF^#, Wang HB, Zhang Y, Chen T, Zheng P, Lu XH, Chen LL* and Yang L*. 2014. Species-specific alternative splicing leads to unique expression of sno-lncRNAs. BMC Genomics, 15(1):287.
60. Yang L* and Chen LL*. 2014. Competition of RNA splicing: line in or circle up. Sci China Life Sci, 57(12):1232-1233.
61. Zhang Y^#, Zhang XO^#, Chen T, Xiang JF, Yin QF, Xing YH, Zhu S, Yang L* and Chen LL*. 2013. Circular intronic long noncoding RNAs. Mol Cell, 51(6):792-806. (Preview by Bolisetty MT and Graveley BR. Mol Cell, 2013, 51:705-706; Research highlights by Nature, 2013, 501:464, Nature China, 2013, doi:10.1038; the mostdownloaded article of the month in Mol Cell).
62. Zhu SS^#, Xiang JF^#, Chen T, Chen LL* and Yang L*. 2013. Prediction of constitutive A-to-I editing sites from human transcriptomes in the absence of genomic sequences. BMC Genomics, 14(1):206.
63. Yin QF^#, Yang L^#, Zhang Y, Xiang JF, Wu YW, Carmichael GG* and Chen LL*. 2012. Long noncoding RNAs with snoRNA ends. Mol Cell, 48(2):219-230. (Cover article; Preview by McCann KL and Baserga SJ. Mol Cell, 2012, 48:155-7; Research highlights by Nat Rev Mol Cell Biol, 2012, 13:686; Five recommendations in F1000 Prime; News coverage in Foundation for Prader-Willi Research; Best of Mol Cell 2012).
64. Yang L, Duff MO, Graveley BR, Carmichael GG and Chen LL*. 2011. Genomewide characterization of non-polyadenylated RNAs. Genome Biol, 12(2):R16. (Editor's pick; Highly accessed).

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