Lynch Lab Publications:

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• Blake D, Gazzara MR, Breuer I, Ferretti M, Lynch KW. (2024) Alternative 3'UTR expression induced by T cell activation is regulated in a temporal and signal dependent manner. Scientific Reports doi: 10.1038/s41598-024-61951-1.

• Liu X, Devadiga SA, Stanley RF, Morrow R, Janssen K, Quesnel-Vallières M, Pomp O, Moverley AA, Li C, Skuli N, Carroll MP, Huang J, Wallace DC, Lynch KW, Abdel-Wahab O, Klein PS. (2024) A mitochondrial surveillance mechanism activated by SRSF2 mutations in hematologic malignancies. JCI doi: 10.1101/2023.06.25.546449.

• Quesnel-Vallières M, Jewell S, Lynch KW, Thomas-Tikhonenko A, Barash Y. (2024) MAJIQlopedia: an encyclopedia of RNA splicing variations in human tissues and cancer. Nucleic Acids Res. doi: 10.1093/nar/gkad1043.

• Hogan MJ, Maheshwari N, Begg BE, Nicastri A, Hedgepeth EJ, Muramatsu H, Pardi N, Miller MA, Reilly SP, Brossay L, Lynch KW, Ternette N, Eisenlohr LC. (2023) Cryptic MHC-E epitope from influenza elicits a potent cytolytic T cell response. Nat Immunol. doi: 10.1038/s41590-023-01644-5.

• Xie Y, Gao S, Zhang K, Bhat P, Clarke BP, Batten K, Mei M, Gazzara M, Shay JW, Lynch KW, Angelos AE, Hill PS, Ivey AL, Fontoura BMA, Ren Y. (2023) Structural basis for high-order complex of SARNP and DDX39B to facilitate mRNP assembly. Cell Rep. doi: 10.1016/j.celrep.2023.112988.

• Bhat P, Aksenova V, Gazzara M, Rex EA, Aslam S, Haddad C, Gao S, Esparza M, Cagatay T, Batten K, El Zahed SS, Arnaoutov A, Zhong H, Shay JW, Tolbert BS, Dasso M, Lynch KW, García-Sastre A, Fontoura BMA. (2023) Influenza virus mRNAs encode determinants for nuclear export via the cellular TREX-2 complex. Nat Commun. doi: 10.1038/s41467-023-37911-0.

• Agosto LM, Mallory MJ, Ferretti MB, Blake D, Krick KS, Gazzara MR, Garcia BA, Lynch KW. (2023) Alternative splicing of HDAC7 regulates its interaction with 14-3-3 proteins to alter histone marks and target gene expression. Cell Rep. doi: 10.1016/j.celrep.2023.112273.

• Burke JM, Ripin N, Ferretti MB, St Clair LA, Worden-Sapper ER, Salgado F, Sawyer SL, Perera R, Lynch KW, Parker R. (2022) RNase L activation in the cytoplasm induces aberrant processing of mRNAs in the nucleus. PLoS Pathog. doi: 10.1371/journal.ppat.1010930.

• Blake D, Radens CM, Ferretti MB, Gazzara MR, Lynch KW. (2022) Alternative splicing of apoptosis genes promotes human T cell survival. Elife. doi: 10.7554/eLife.80953.

• Peart NJ, Hwang JY, Quesnel-Vallières M, Sears MJ, Yang Y, Stoilov P, Barash Y, Park JW, Lynch KW, Carstens RP. (2022) The global Protein-RNA interaction map of ESRP1 defines a post-transcriptional program that is essential for epithelial cell function. iScience. doi: 10.1016/j.isci.2022.105205.

• Basavappa MG, Ferretti M, Dittmar M, Stoute J, Sullivan MC, Whig K, Shen H, Liu KF, Schultz DC, Beiting DP, Lynch KW, Henao-Mejia J, Cherry S. (2022) The lncRNA ALPHA specifically targets chikungunya virus to control infection. Mol Cell. doi: 10.1016/j.molcel.2022.08.030.

• Gao S, Esparza M, Dehghan I, Aksenova V, Zhang K, Batten K, Ferretti MB, Begg BE, Cagatay T, Shay JW, García-Sastre A, Goldsmith EJ, Chen ZJ, Dasso M, Lynch KW, Cobb MH, Fontoura BMA. (2022) Nuclear speckle integrity and function require TAO2 kinase. Proc Natl Acad Sci U S A. doi: 10.1073/pnas.2206046119.

• Jha A, Quesnel-Vallières M, Wang D, Thomas-Tikhonenko A, Lynch KW, Barash Y. (2022) Identifying common transcriptome signatures of cancer by interpreting deep learning models. Genome Biol. doi: 10.1186/s13059-022-02681-3.

• Zheng S, Gillespie E, Naqvi AS, Hayer KE, Ang Z, Torres-Diz M, Quesnel-Vallières M, Hottman DA, Bagashev A, Chukinas J, Schmidt C, Asnani M, Shraim R, Taylor DM, Rheingold SR, O'Brien MM, Singh N, Lynch KW, Ruella M, Barash Y, Tasian SK, Thomas-Tikhonenko A (2021) Modulation of CD22 Protein Expression in Childhood Leukemia by Pervasive Splicing Aberrations: Implications for CD22-Directed Immunotherapies. Blood Cancer Discov. doi: 10.1158/2643-3230.BCD-21-0087.

• Blake, D, Lynch KW (2021) The three As: Alternative splicing, alternative polyadenylation and their impact on apoptosis in immune function. Immunol Rev. 304:30-50. doi: 10.1111/imr.13018.

• Sengupta S, West KO, Sanghvi S, Laliotis G, Agosto LM, Lynch KW, Tsichlis PN, Singh H, Patrick KL, Guerau-de-Arellano M. (2021) PRMT5 Promotes Symmetric Dimethylation of RNA Processing Proteins and Modulates Activated T Cell Alternative Splicing and Ca2+/NFAT Signaling. Immunohorizons 5:884-897. doi: 10.4049/immunohorizons.2100076.

• Slaff B, Radens CM, Jewell P, Jha A, Lahens NF, Grant GR, Thomas-Tikhonenko A, Lynch KW, Barash Y (2021) MOCCASIN: a method for correcting for known and unknown confounders in RNA splicing analysis Nat Commun. 12:3353. doi: 10.1038/s41467-021-23608-9.

• Rivera OD, Mallory MJ, Quesnel-Vallières M, Chatrikhi R, Schultz DC, Carroll M, Barash Y, Cherry S, Lynch KW. (2021) Alternative splicing redefines landscape of commonly mutated genes in acute myeloid leukemia. Proc Natl Acad Sci U S A. 118: e2014967118. doi: 10.1073/pnas.2014967118.

• Thompson MG, Dittmar M, Mallory MJ, Bhat P, Ferretti MB, Fontoura BM, Cherry S, Lynch KW. (2020) Viral-induced alternative splicing of host genes promotes influenza replication. Elife 9:e55500. doi: 10.7554/eLife.55500.

• Cherry S and Lynch KW. (2020) Alternative Splicing and Cancer: Insights, Opportunities and Challenges from an Expanding View of the Transcriptome. Genes Dev. 34: 1005-1016. doi: 10.1101/gad.338962.120. (PDF)

• Radens CM, Blake D, Jewell P, Barash Y, Lynch KW. (2020) Meta-Analysis of Transcriptomic Variation in T cell Populations Reveals both Variable and Consistent Signatures of Gene Expression and Splicing. RNA 26:1320-1333. doi: 10.1261/rna.075929.120. (PDF)

• Mallory MJ, McClory SP, Chatrikhi R, Gazzara MR, Ontiveros RJ, Lynch, KW. (2020) Reciprocal regulation of hnRNP C and CELF2 through translation and transcription tunes splicing activity in T cells. Nucleic Acids Res. 48: 5710-5719. doi: 10.1093/nar/gkaa295. (PDF)

• Thompson, MG, Lynch, KW. (2019) Functional and Mechanistic Interplay of Host and Viral Alternative Splicing Regulation during Influenza Infection. Cold Spring Harbor Symposia on Quantitative Biology 84:123-131. doi:10.1101/sqb.2019.84.039040. (PDF)

• Agosto LM, Gazzara MR, Radens CM, Sidoli S, Baeza J, Garcia BA, Lynch KW. (2019) Deep profiling and custom databases improve detection of proteoforms generated by alternative splicing. Genome Res. 29:2046-2055. doi: 10.1101/gr.248435.119. (PDF)

• Chatrikhi R, Mallory MJ, Gazzara MR, Agosto LM, Zhu WS, Litterman AJ, Ansel KM, Lynch KW. (2019) RNA Binding Protein CELF2 Regulates Signal-Induced Alternative Polyadenylation by Competing with Enhancers of the Polyadenylation Machinery. Cell Rep. 28:2795-2806.e3. doi: 10.1016/j.celrep.2019.08.022. (PDF)

• Zhang K, Shang G, Padavannil A, Wang J, Sakthivel R, Chen X, Kim M, Thompson MG, García-Sastre A, Lynch KW, Chen ZJ, Chook YM, Fontoura BMA. (2018) Structural-functional interactions of NS1-BP protein with the splicing and mRNA export machineries for viral and host gene expression. Proc Natl Acad Sci U S A. 115:E12218-E12227. doi: 10.1073/pnas.1818012115. (PDF)

• Black KL, Naqvi AS, Asnani M, Hayer KE, Yang SY, Gillespie E, Bagashev A, Pillai V, Tasian SK, Gazzara MR, Carroll M, Taylor D, Lynch KW, Barash Y, Thomas-Tikhonenko A. (2018) Aberrant splicing in B-cell acute lymphoblastic leukemia. Nucleic Acids Res. 46:1357-11369. doi: 10.1093/nar/gky946. (PDF)

• Thompson MG, Munoz-Moreno R, Bhat P, Roytenberg R, Linberg J, Gazzara MR, Mallory MJ, Zhang K, Garcia-Sastre A, Fontoura BMA, Lynch KW. (2018) Co-Regulatory activity of hnRNP K and NS1-BP in influenza and human mRNA splicing. Nat Commun. 9(1):2407. doi: 10.1038/s41467-018-04779-4. (PDF)

• McClory SP, Lynch KW, Ling JP. (2018) HnRNP L represses cryptic exons. RNA. 24(6):761-768. doi: 10.1261/rna.065508.117. (PDF)

• Shinde MY, Sidoli S, Kulej K, Mallory MJ, Radens CM, Reicherter AL, Myers RL, Barash Y, Lynch KW, Garcia BA, Klein PS. (2017) Phosphoproteomics reveals that glycogen synthase kinase-3 phosphorylates multiple splicing factors and is associated with alternative splicing. J Biol Chem. 292(44):18240-18255. doi: 10.1074/jbc.M117.813527. (PDF)

• Gazzara MR, Mallory MJ, Roytenberg R, Lindberg JP, Jha A, Lynch KW, Barash Y. (2017) Ancient antagonism between CELF and RBFOX families tunes mRNA splicing outcomes. Genome Res. 27(8):1360. doi: 10.1101/gr.220517.117. (PDF) 

• Mor A, White A, Zhank K, THompson M, Esparza M, Munoz-Moreno R, Koide K, Lynch KW, Garcia-Sastre A, Fontoura BM. (2016) Influenza virus mRNA trafficking through host nuclear speckles. Nat Microbiol. 1(7):16069. doi: 10.1038/nmicrobiol.2016.69. (PDF)

• Ajith S, Gazzara MR, Cole BS, Shankarling G, Martinez NM, Mallory MJ, Lynch KW. (2016) Position-dependent activity of CELF2 in the regulation of splicing and implications for signal-responsive regulation in T cells. RNA Biology. 13(5):1-13. (PDF)

• Vaquero-Garcia J, Barrera A, Gazzara MR, Gonzalez-Vallinas J, Lahens NF, Hogenesch JB, Lynch KW, Barash Y. (2016) A new view of transcriptome complexity and regulation through the lens of local splicing variations. eLife.5:e11752. (PDF)

• Sotillo E, Barrett DM, Black KL, Bagashev A, Oldridge D, Wu G, Sussman R, Lanauze C, Ruella M, Gazzara MR, Martinez NM, Harrington CT, Chung EY, Perazzelli J, Hofmann TJ, Maude SL, Raman P, Barrera A, Gill S, Lacey SF, Melenhorst JJ, Allman D, Jacoby E, Fry T, Mackall C, Barash Y, Lynch KW, Maris JM, Grupp SA, Thomas-Tikhonenko A. (2015) Convergence of Acquired Mutations and Alternative Splicing of CD19 Enables Resistance to CART-19 Immunotherapy. Cancer Discov. 5(12):1282-95. (PDF)

• Martinez NM, Agosto L, Qiu J, Mallory MJ, Gazzara MR, Barash Y, Fu XD, Lynch KW. (2015) Widespread JNK-dependent alternative splicing induces a positive feedback loop through CELF2-mediated regulation of MKK7 during T-cell activation. Genes Dev. 29(19):2054-66. (PDF)

• Cole BS, Tapescu I, Allon SJ, Mallory MJ, Qiu J, Lake RJ, Fan HY, Fu XD, Lynch KW. (2015) Global analysis of physical and functional RNA targets of hnRNP L reveals distinct sequence and epigenetic features of repressed and enhanced exons. RNA 21:1-14. (PDF)

• Yarosh CA, Tapescu I, Thompson MG, Qiu J, Mallory MJ, Fu XD, Lynch KW. (2015) TRAP150 interacts with the RNA-binding domain of PSF and antagonizes splicing of numerous PSF-target genes in T cells. Nucleic Acids Res. 43(18):9006-16.(PDF)

• Mallory MJ, Allon SJ, Qiu J, Gazzara MR, Tapescu I, Martinez NM, Fu XD, Lynch KW. (2015) Induced transcription and stability of CELF2 mRNA drives widespread alternative splicing during T-cell signaling. Proc. Natl. Acad. Sci.122(17):E2139-48. (PDF)

• Yarosh CA, Iacona JR, Lutz CS, Lynch KW. (2015) PSF: nuclear busy-body or nuclear facilitator? WIREs RNA 6:351-67. (PDF)

• Lynch KW. (2015) Thoughts on NGS, alternative splicing and what we still need to know. RNA 21(4):683-4. (PDF)

• Moy RH, Cole BS, Yasunaga A, Gold B, Shankarling G, Varble A, Molleston JM, tenOever BR, Lynch KW, Cherry S. (2014) Stem-Loop Recognition by DDX17 Facilitates miRNA Processing and Antiviral Defense. Cell 158(4):764-77. (PDF)

• Smith SA, Lynch KW. (2014) Cell-based splicing of minigenes. Methods Mol Biol1126:243-55. (PDF)

• Chiou NT, Lynch KW. (2014) Mechanisms of spliceosomal assembly. Methods Mol Biol 1126:35-43. (PDF)

• Motta-Mena LB, Reade A, Mallory MJ, Glantz S, Weiner OD, Lynch KW, Gardner KH. (2014) An optogenetic gene expression system with rapid activation and deactivation kinetics. Nat Chem Biol 10(3):196-202. (PDF)

• Gazzara MR, Vaquero-Garcia J, Lynch KW, Barash Y. (2014) In silico to in vivo splicing analysis using splicing code models. Methods 67(1):3-12. (PDF)

• Smith SA, Ray D, Cook KB, Mallory MJ, Hughes TR, Lynch KW. (2013) Paralogs hnRNP L and hnRNP LL exhibit overlapping but distinct RNA binding constraints. PLoS One 8(11):e80701 (PDF)

• Shankarling G, Cole BS, Mallory MJ, Lynch KW. (2014) Transcriptome-wide RNA interaction profiling reveals physical and functional targets of hnRNP L in human T cells. Mol Cell Biol 34(1):71-83. (PDF)

• Ray D, Kazan H, Cook KB, Weirauch MT, Najafabadi HS, Li X, Gueroussov S, Albu M, Zheng H, Yang A, Na H, Irimia M, Matzat LH, Dale RK, Smith SA, Yarosh CA, Kelly SM, Nabet B, Mecenas D, Li W, Laishram RS, Qiao M, Lipshitz HD, Piano F, Corbett AH, Carstens RP, Frey BJ, Anderson RA, Lynch KW, Penalva LO, Lei EP, Fraser AG, Blencowe BJ, Morris QD, Hughes TR. (2013) A compendium of RNA-binding motifs for decoding gene regulation. Nature499(7457):172-7. (PDF)

• Tsai PL, Chiou NT, Kuss S, García-Sastre A, Lynch KW, Fontoura BM. (2013) Cellular RNA binding proteins NS1-BP and hnRNP K regulate influenza A virus RNA splicing. PLoS Pathog. 9(6):e1003460. (PDF)

• Shankarling G, Lynch KW. (2013) Minimal functional domains of paralogues hnRNP L and hnRNP LL exhibit mechanistic differences in exonic splicing repression. Biochem J. 453(2):271-9. (PDF)

• Martinez NM, Lynch KW. (2013) Control of alternative splicing in immune responses: many regulators, many predictions, much still to learn. Immunol Rev. 253(1):216-36. (PDF)

• Vu NT, Park MA, Shultz JC, Goehe RW, Hoeferlin LA, Shultz MD, Smith SA, Lynch KW, Chalfant CE. (2013) hnRNP U enhances caspase-9 splicing and is modulated by AKT-dependent phosphorylation of hnRNP L. J Biol Chem.288(12):8575-84. (PDF)

• Chiou NT, Shankarling G, Lynch KW. (2013) hnRNP L and hnRNP A1 induce extended U1 snRNA interactions with an exon to repress spliceosome assembly. Mol Cell. 49(5):972-82. (PDF)

• Martinez NM, Pan Q, Cole BS, Yarosh CA, Babcock GA, Heyd F, Zhu W, Ajith S, Blencowe BJ, Lynch KW. (2012) Alternative splicing networks regulated by signaling in human T cells. RNA. 18(5):1029-40. (PDF)

• Heyd F, Lynch KW. (2011) DEGRADE, MOVE, REGROUP: signaling control of splicing proteins. Trends Biochem Sci. 36(8):397-404. (PDF)

• Motta-Mena LB, Smith SA, Mallory MJ, Jackson J, Wang J, Lynch KW. (2011) A disease-associated polymorphism alters splicing of the human CD45 phosphatase gene by disrupting combinatorial repression by heterogeneous nuclear ribonucleoproteins (hnRNPs). J Biol Chem. 286(22):20043-53. (PDF)

• Mallory MJ, Jackson J, Weber B, Chi A, Heyd F, Lynch KW. (2011) Signal- and development-dependent alternative splicing of LEF1 in T cells is controlled by CELF2. Mol Cell Biol. 31(11):2184-95. (PDF)

• Shankarling G., Lynch K.W. (2010) Living or dying by RNA processing: caspase expression in NSCLC. J Clin Invest. 120(11):3798-801. (PDF)

• Heyd F., Lynch K.W. (2010) Phosphorylation-dependent regulation of PSF by GSK3 controls CD45 alternative splicing. Mol Cell. 40(1):126-37. (PDF)

• Motta-Mena L., Heyd F., and K.W. Lynch (2010) Context-dependent regulatory mechanism of the splicing factor hnRNP L. Mol Cell. 37(2):223-34. (PDF)

• Heyd F, Lynch K.W. (2009) Getting under the skin of alternative splicing: identification of epithelial-specific splicing factors. Mol Cell. 33(6):674-6. (PDF)

• Topp, J.D., Jackson, J, Melton, A.A. and K.W. Lynch (2008) A cell-based screen for splicing regulators identifies hnRNP LL as an additional signal-induced repressor of CD45 variable exon 4. RNA 14: 2038-2049. (PDF)

• House, A.E. and K.W. Lynch (2008) Regulation of Alternative Splicing: More than just the ABCs. J. Biol. Chem. 283: 1217-21. (PDF)

• Melton, A.A., Jackson, J.M., Wang, J. and K.W. Lynch (2007) Combinatorial control of signal-induced exon repression by HnRNP L and PSF. Mol. Cell. Biol.27, 6972-6984. (PDF)

• Lynch, K.W. (2007) Regulation of alternative splicing by signal transduction pathways. In Alternative Splicing in the Postgenomic Era edited by B. Blencowe and B. Graveley. Eurekah Biosciences Press and Lander Press. Adv Exp Med Biol. 623:161-74. (PDF)

• Ip, J., A. Tong, Q. Pan, J. Topp, B.J. Blencowe* and K.W. Lynch. (2007) Global analysis of alternative splicing during T cell activation. RNA 13:563-572. (* co-corresponding authors) (PDF)

• Lynch K.W. (2006) Cotranscriptional splicing regulation: it's not just about speed.Nat Struct Mol Biol 13(11):952-3. (PDF)

• House, A.E. and K.W. Lynch. (2006) An exonic splicing silencer represses spliceosome assembly after ATP-dependent exon recognition. Nat. Struct. Mol. Biol., 13:937-944. (PDF)

• Johnson, E.B., D.J. Steffen, K.W. Lynch, and J. Herz. (2006) Defective splicing of MEGF7/LRP4, a regulator of distal limb development, in autosomal recessive Mulefoot disease. Genomics 88: 600-609. (PDF)

• Levinson, N., R. Hinman, A. Patil, C.R.J. Stephenson, S. Werner, G.H.C. Woo, J. Xiao, P. Wipf and K.W. Lynch (2006) Use of transcriptional synergy to augment sensitivity of a splicing reporter assay. RNA 12: 925-930 (PDF)

• Tong, A., J. Nguyen and K.W. Lynch (2005) Differential expression of CF45 isoforms is controlled by the combined activity of basal and inducible splicing regulatory elements in each of the variable exons. J. Biol. Chem. 280:38297-304. (PDF)

• Rothrock, C.R.*, A.E. House*, and K.W. Lynch (2005) HnRNP L represses exon splicing via a regulated exonic splicing silencer. EMBO J 24: 2792-2802. (* co-first authors) (PDF)

• Lynch, K.W. (2004) Consequences of regulated pre-mRNA splicing in the immune system. Nat Rev Immunol. 4: 931-940. (PDF)

• Rothrock, C., B. Cannon, B. Hahm and K.W. Lynch (2003) A conserved signal-responsive sequence mediates activation-induced alternative splicing of CD45. Mol. Cell 12: 1317-1324. (PDF)

• Sheives, P. and K.W. Lynch (2002) Identification of cells deficient in signaling-induced alternative splicing by use of somatic-cell genetics. RNA 8:1473-1481. (No PDF available)

• Lynch, K.W. and A. Weiss (2001) A CD45 polymorphism associated with multiple sclerosis disrupts an exonic splicing silencer. J. Biol. Chem. 276: 24341-24347. (PDF)

• Lynch, K.W. and A. Weiss (2000) A model system for activation-induced alternative splicing of CD45 pre-mRNA in T cells implicates protein kinase C and Ras. Mol Cell Biol 20:70-80. (No PDF available)

• Hertel, K.J., K.W. Lynch and T. Maniatis (1997) Common themes in the function of transcription and splicing enhancers. Curr Opin Cell Biol. 9:350-357. (PDF)

• Hertel, K.J., K.W. Lynch, E.C. Hsiao, E.H.-T. Liu and T. Maniatis (1996) Structural and functional conservation of the Drosophila doublesex splicing enhancer repeat elements. RNA 2:969-981. (PDF)

• Lynch, K.W. and T. Maniatis (1996) Assembly of specific SR protein complexes on distinct regulatory elements of the Drosophila doublesex splicing enhancer.Genes and Dev. 10:2089-2101. (PDF)

• Lynch, K.W. and T. Maniatis (1995) Synergistic interactions between two distinct elements of a regulated splicing enhancer. Genes and Dev. 9:284-293. (PDF)

• Sadowski, I., D. Neidbala, K. Wood and M. Ptashne (1991) Gal4 is phosphorylated as as consequence of transcriptional activation. Proc. Natl. Acad. Sci. USA 88: 10510-10514. (No PDF available)

• Ruden, D.M., J. Ma, Y. Li, K. Wood and M. Ptashne (1991) Generating yeast transcriptional activators containing no yeast protein sequences. Nature 350: 250-252. (No PDF available)