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New Links between mRNA Polyadenylation and Diverse Nuclear Pathways

  • Di Giammartino, Dafne Campigli (Columbia University, Department of Biological Sciences) ;
  • Manley, James L. (Columbia University, Department of Biological Sciences)
  • Received : 2014.06.25
  • Accepted : 2014.06.28
  • Published : 2014.09.30

Abstract

The 3' ends of most eukaryotic messenger RNAs must undergo a maturation step that includes an endonuc-leolytic cleavage followed by addition of a polyadenylate tail. While this reaction is catalyzed by the action of only two enzymes it is supported by an unexpectedly large number of proteins. This complexity reflects the necessity of coordinating this process with other nuclear events, and growing evidence indicates that even more factors than previously thought are necessary to connect 3' processing to additional cellular pathways. In this review we summarize the current understanding of the molecular machinery involved in this step of mRNA maturation, focusing on new core and auxiliary proteins that connect polyadenylation to splicing, DNA damage, transcription and cancer.

Keywords

References

  1. Almada, A.E., Wu, X., Kriz, A.J., Burge, C.B., and Sharp, P.A. (2013). Promoter directionality is controlled by U1 snRNP and polyadenylation signals. Nature 499, 360-363. https://doi.org/10.1038/nature12349
  2. Ariumi, Y., Masutani, M., Copeland, T.D., Mimori, T., Sugimura, T., Shimotohno, K., Ueda, K., Hatanaka, M., and Noda, M. (1999). Suppression of the poly(ADP-ribose) polymerase activity by DNA-dependent protein kinase in vitro. Oncogene 18, 4616-4625. https://doi.org/10.1038/sj.onc.1202823
  3. Awasthi, S., and Alwine, J.C. (2003). Association of polyadenylation cleavage factor I with U1 snRNP. RNA 9, 1400-1409. https://doi.org/10.1261/rna.5104603
  4. Baillat, D., Hakimi, M.A., Naar, A.M., Shilatifard, A., Cooch, N., and Shiekhattar, R. (2005). Integrator, a multiprotein mediator of small nuclear RNA processing, associates with the C-terminal repeat of RNA polymerase II. Cell 123, 265-276. https://doi.org/10.1016/j.cell.2005.08.019
  5. Berglund, J.A., Chua, K., Abovich, N., Reed, R., and Rosbash, M. (1997). The splicing factor BBP interacts specifically with the premRNA branchpoint sequence UACUAAC. Cell 89, 781-787. https://doi.org/10.1016/S0092-8674(00)80261-5
  6. Cevher, M.A., Zhang, X., Fernandez, S., Kim, S., Baquero, J., Nilsson, P., Lee, S., Virtanen, A., and Kleiman, F.E. (2010). Nuclear deadenylation/polyadenylation factors regulate 3' processing in response to DNA damage. EMBO J. 29, 1674-1687. https://doi.org/10.1038/emboj.2010.59
  7. Colgan, D.F., Murthy, K.G., Prives, C., and Manley, J.L. (1996). Cellcycle related regulation of poly(A) polymerase by phosphorylation. Nature 384, 282-285. https://doi.org/10.1038/384282a0
  8. Collis, S.J., DeWeese, T.L., Jeggo, P.A., and Parker, A.R. (2005). The life and death of DNA-PK. Oncogene 24, 949-961. https://doi.org/10.1038/sj.onc.1208332
  9. Davidson, D., Amrein, L., Panasci, L., and Aloyz, R. (2013). Small molecules, inhibitors of DNA-PK, targeting DNA repair, and beyond. Front. Pharmacol. 4, 5.
  10. Di Giammartino, D.C., Nishida, K., and Manley, J.L. (2011). Mechanisms and consequences of alternative polyadenylation. Mol. Cell 43, 853-866. https://doi.org/10.1016/j.molcel.2011.08.017
  11. Di Giammartino, D.C., Shi, Y., and Manley, J.L. (2013). PARP1 represses PAP and inhibits polyadenylation during heat shock. Mol. Cell 49, 7-17. https://doi.org/10.1016/j.molcel.2012.11.005
  12. Elkon, R., Ugalde, A.P., and Agami, R. (2013). Alternative cleavage and polyadenylation: extent, regulation and function. Nat. Rev. Genet. 14, 496-506. https://doi.org/10.1038/nrg3482
  13. Gilbert, W., and Guthrie, C. (2004). The Glc7p nuclear phosphatase promotes mRNA export by facilitating association of Mex67p with mRNA. Mol. Cell 13, 201-212. https://doi.org/10.1016/S1097-2765(04)00030-9
  14. Gozani, O., Feld, R., and Reed, R. (1996). Evidence that sequenceindependent binding of highly conserved U2 snRNP proteins upstream of the branch site is required for assembly of spliceosomal complex A. Genes Dev. 10, 233-243. https://doi.org/10.1101/gad.10.2.233
  15. Gunderson, S.I., Polycarpou-Schwarz, M., and Mattaj, I.W. (1998). U1 snRNP inhibits pre-mRNA polyadenylation through a direct interaction between U1 70K and poly(A) polymerase. Mol. Cell 1, 255-264. https://doi.org/10.1016/S1097-2765(00)80026-X
  16. He, X., and Moore, C. (2005). Regulation of yeast mRNA 3' end processing by phosphorylation. Mol. Cell 19, 619-629. https://doi.org/10.1016/j.molcel.2005.07.016
  17. Hu, J., Lutz, C.S., Wilusz, J., and Tian, B. (2005). Bioinformatic identification of candidate cis-regulatory elements involved in human mRNA polyadenylation. RNA 11, 1485-1493. https://doi.org/10.1261/rna.2107305
  18. Ji, Z., and Tian, B. (2009). Reprogramming of 3' untranslated regions of mRNAs by alternative polyadenylation in generation of pluripotent stem cells from different cell types. PLoS One 4, e8419. https://doi.org/10.1371/journal.pone.0008419
  19. Ji, Y., and Tulin, A.V. (2010). The roles of PARP1 in gene control and cell differentiation. Curr. Opin. Genet. Dev. 20, 512-518. https://doi.org/10.1016/j.gde.2010.06.001
  20. Ji, Z., Lee, J.Y., Pan, Z., Jiang, B., and Tian, B. (2009). Progressive lengthening of 3' untranslated regions of mRNAs by alternative polyadenylation during mouse embryonic development. Proc. Natl. Acad. Sci. USA 106, 7028-7033. https://doi.org/10.1073/pnas.0900028106
  21. Jungmichel, S., Rosenthal, F., Altmeyer, M., Lukas, J., Hottiger, M.O., and Nielsen, M.L. (2013). Proteome-wide identification of poly(ADP-Ribosyl)ation targets in different genotoxic stress responses. Mol. Cell 52, 272-285. https://doi.org/10.1016/j.molcel.2013.08.026
  22. Kapp, L.D., Abrams, E.W., Marlow, F.L., and Mullins, M.C. (2013). The integrator complex subunit 6 (Ints6) confines the dorsal organizer in vertebrate embryogenesis. PLoS Genet. 9, e1003822. https://doi.org/10.1371/journal.pgen.1003822
  23. Kim, Y.M., Watanabe, T., Allen, P.B., Kim, Y.M., Lee, S.J., Greengard, P., Nairn, A.C., and Kwon, Y.G. (2003). PNUTS, a protein phosphatase 1 (PP1) nuclear targeting subunit. Characterization of its PP1- and RNA-binding domains and regulation by phosphorylation. J. Biol. Chem. 278, 13819-13828 https://doi.org/10.1074/jbc.M209621200
  24. Kleiman, F.E., and Manley, J.L. (1999). Functional interaction of BRCA1-associated BARD1 with polyadenylation factor CstF-50. Science 285, 1576-1579. https://doi.org/10.1126/science.285.5433.1576
  25. Kleiman, F.E., and Manley, J.L. (2001). The BARD1-CstF-50 interaction links mRNA 3' end formation to DNA damage and tumor suppression. Cell 104, 743-753. https://doi.org/10.1016/S0092-8674(01)00270-7
  26. Krishnakumar, R., and Kraus, W.L. (2010). The PARP side of the nucleus: molecular actions, physiological outcomes, and clinical targets. Mol. Cell 39, 8-24. https://doi.org/10.1016/j.molcel.2010.06.017
  27. Lackford, B., Yao, C., Charles, G.M., Weng, L., Zheng, X., Choi, E.A., Xie, X., Wan, J., Xing, Y., Freudenberg, J.M., et al. (2014). Fip1 regulates mRNA alternative polyadenylation to promote stem cell self-renewal. EMBO J. 33, 878-889. https://doi.org/10.1002/embj.201386537
  28. Li, W., Yeh, H.J., Shankarling, G.S., Ji, Z., Tian, B., and MacDonald, C.C. (2012). The tauCstF-64 polyadenylation protein controls genome expression in testis. PLoS One 7, e48373. https://doi.org/10.1371/journal.pone.0048373
  29. Lubas, M., Christensen, M.S., Kristiansen, M.S., Domanski, M., Falkenby, L.G., Lykke-Andersen, S., Andersen, J.S., Dziembowski, A., and Jensen, T.H. (2011). Interaction profiling identifies the human nuclear exosome targeting complex. Mol. Cell 43, 624-637.
  30. Mandel, C.R., Bai, Y., and Tong, L. (2008). Protein factors in premRNA 3'-end processing. Cell. Mol. Life Sci. 65, 1099-1122. https://doi.org/10.1007/s00018-007-7474-3
  31. Mayr, C., and Bartel, D.P. (2009). Widespread shortening of 3'UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells. Cell 138, 673-684. https://doi.org/10.1016/j.cell.2009.06.016
  32. Mbita, Z., Meyer, M., Skepu, A., Hosie, M., Rees, J., and Dlamini, Z. (2012). De-regulation of the RBBP6 isoform 3/DWNN in human cancers. Mol. Cell. Biochem. 362, 249-262. https://doi.org/10.1007/s11010-011-1150-5
  33. Meinhart, A., and Cramer, P. (2004). Recognition of RNA polymerase II carboxy-terminal domain by 3'-RNA-processing factors. Nature 430, 223-226. https://doi.org/10.1038/nature02679
  34. Mueller, C.L., Porter, S.E., Hoffman, M.G., and Jaehning, J.A. (2004). The Paf1 complex has functions independent of actively transcribing RNA polymerase II. Mol. Cell 14, 447-456. https://doi.org/10.1016/S1097-2765(04)00257-6
  35. Nagaike, T., Logan, C., Hotta, I., Rozenblatt-Rosen, O., Meyerson, M., and Manley, J.L. (2011). Transcriptional activators enhance polyadenylation of mRNA precursors. Mol. Cell 41, 409-418. https://doi.org/10.1016/j.molcel.2011.01.022
  36. Nazeer, F.I., Devany, E., Mohammed, S., Fonseca, D., Akukwe, B., Taveras, C., and Kleiman, F.E. (2011). p53 inhibits mRNA 3' processing through its interaction with the CstF/BARD1 complex. Oncogene 30, 3073-3083. https://doi.org/10.1038/onc.2011.29
  37. Ntini, E., Jarvelin, A.I., Bornholdt, J., Chen, Y., Boyd, M., Jorgensen, M., Andersson, R., Hoof, I., Schein, A., Andersen, P.R., et al. (2013). Polyadenylation site-induced decay of upstream transcripts enforces promoter directionality. Nat. Struct. Mol. Biol. 20, 923-928. https://doi.org/10.1038/nsmb.2640
  38. Ohnacker, M., Barabino, S.M., Preker, P.J., and Keller, W. (2000). The WD-repeat protein pfs2p bridges two essential factors within the yeast pre-mRNA 3'-end-processing complex. EMBO J. 19, 37-47. https://doi.org/10.1093/emboj/19.1.37
  39. Pashkova, N., Gakhar, L., Winistorfer, S.C., Yu, L., Ramaswamy, S., and Piper, R.C. (2010). WD40 repeat propellers define a ubiquitin-binding domain that regulates turnover of F box proteins. Mol. Cell 40, 433-443. https://doi.org/10.1016/j.molcel.2010.10.018
  40. Penheiter, K.L., Washburn, T.M., Porter, S.E., Hoffman, M.G., and Jaehning, J.A. (2005). A posttranscriptional role for the yeast Paf1-RNA polymerase II complex is revealed by identification of primary targets. Mol. Cell 20, 213-223. https://doi.org/10.1016/j.molcel.2005.08.023
  41. Proudfoot, N.J. (2011). Ending the message: poly(A) signals then and now. Genes Dev. 25, 1770-1782. https://doi.org/10.1101/gad.17268411
  42. Reinhardt, H.C., and Yaffe, M.B. (2013). Phospho-Ser/Thr-binding domains: navigating the cell cycle and DNA damage response. Nat. Rev. Mol. Cell Biol. 14, 563-580. https://doi.org/10.1038/nrm3640
  43. Rozenblatt-Rosen, O., Nagaike, T., Francis, J.M., Kaneko, S., Glatt, K.A., Hughes, C.M., LaFramboise, T., Manley, J.L., and Meyerson, M. (2009). The tumor suppressor Cdc73 functionally associates with CPSF and CstF 3'mRNA processing factors. Proc. Natl. Acad. Sci. USA 106, 755-760. https://doi.org/10.1073/pnas.0812023106
  44. Ryan, K., and Bauer, D.L. (2008). Finishing touches: posttranslational modification of protein factors involved in mammalian pre-mRNA 3' end formation. Int. J. Biochem. Cell Biol. 40, 2384-2396. https://doi.org/10.1016/j.biocel.2008.03.016
  45. Sakai, Y., Saijo, M., Coelho, K., Kishino, T., Niikawa, N., and Taya, Y. (1995). cDNA sequence and chromosomal localization of a novel human protein, RBQ-1 (RBBP6), that binds to the retinoblastoma gene product. Genomics 30, 98-101. https://doi.org/10.1006/geno.1995.0017
  46. Sandberg, R., Neilson, J.R., Sarma, A., Sharp, P.A., and Burge, C.B. (2008). Proliferating cells express mRNAs with shortened 3' untranslated regions and fewer microRNA target sites. Science 320, 1643-1647. https://doi.org/10.1126/science.1155390
  47. Shi, Y., Reddy, B., and Manley, J.L. (2006). PP1/PP2A phosphatases are required for the second step of Pre-mRNA splicing and target specific snRNP proteins. Mol. Cell 23, 819-829. https://doi.org/10.1016/j.molcel.2006.07.022
  48. Shi, Y., Di Giammartino, D.C., Taylor, D., Sarkeshik, A., Rice, W.J., Yates, J.R., 3rd, Frank, J., and Manley, J.L. (2009). Molecular architecture of the human pre-mRNA 3' processing complex. Mol. Cell 33, 365-376. https://doi.org/10.1016/j.molcel.2008.12.028
  49. Simons, A., Melamed-Bessudo, C., Wolkowicz, R., Sperling, J., Sperling, R., Eisenbach, L., and Rotter, V. (1997). PACT: cloning and characterization of a cellular p53 binding protein that interacts with Rb. Oncogene 14, 145-155. https://doi.org/10.1038/sj.onc.1200825
  50. Stuparevic, I., Mosrin-Huaman, C., Hervouet-Coste, N., Remenaric, M., and Rahmouni, A.R. (2013). Cotranscriptional recruitment of RNA exosome cofactors Rrp47p and Mpp6p and two distinct Trf-Air-Mtr4 polyadenylation (TRAMP) complexes assists the exonuclease Rrp6p in the targeting and degradation of an aberrant messenger ribonucleoprotein particle (mRNP) in yeast. J. Biol. Chem. 288, 31816-31829. https://doi.org/10.1074/jbc.M113.491290
  51. Takagaki, Y., and Manley, J.L. (2000). Complex protein interactions within the human polyadenylation machinery identify a novel component. Mol. Cell. Biol. 20, 1515-1525. https://doi.org/10.1128/MCB.20.5.1515-1525.2000
  52. Takagaki, Y., Ryner, L.C., and Manley, J.L. (1988). Separation and characterization of a poly(A) polymerase and a cleavage/specificity factor required for pre-mRNA polyadenylation. Cell 52, 731-742. https://doi.org/10.1016/0092-8674(88)90411-4
  53. Takata, H., Nishijima, H., Maeshima, K., and Shibahara, K. (2012). The integrator complex is required for integrity of Cajal bodies. J. Cell Sci. 125, 166-175. https://doi.org/10.1242/jcs.090837
  54. Tian, B., and Manley, J.L. (2013). Alternative cleavage and polyadenylation: the long and short of it. Trends Biochem. Sci. 38, 312-320. https://doi.org/10.1016/j.tibs.2013.03.005
  55. Topalian, S.L., Kaneko, S., Gonzales, M.I., Bond, G.L., Ward, Y., and Manley, J.L. (2001). Identification and functional characterization of neo-poly(A) polymerase, an RNA processing enzyme overexpressed in human tumors. Mol. Cell. Biol. 21, 5614-5623. https://doi.org/10.1128/MCB.21.16.5614-5623.2001
  56. Vagner, S., Vagner, C., and Mattaj, I.W. (2000). The carboxyl terminus of vertebrate poly(A) polymerase interacts with U2AF 65 to couple 3'-end processing and splicing. Genes Dev. 14, 403-413.
  57. Vethantham, V., Rao, N., and Manley, J.L. (2008). Sumoylation regulates multiple aspects of mammalian poly(A) polymerase function. Genes Dev. 22, 499-511. https://doi.org/10.1101/gad.1628208
  58. Vo, L.T., Minet, M., Schmitter, J.M., Lacroute, F., and Wyers, F. (2001). Mpe1, a zinc knuckle protein, is an essential component of yeast cleavage and polyadenylation factor required for the cleavage and polyadenylation of mRNA. Mol. Cell. Biol. 21, 8346-8356. https://doi.org/10.1128/MCB.21.24.8346-8356.2001
  59. Wallace, A.M., Dass, B., Ravnik, S.E., Tonk, V., Jenkins, N.A., Gilbert, D.J., Copeland, N.G., and MacDonald, C.C. (1999). Two distinct forms of the 64,000 Mr protein of the cleavage stimulation factor are expressed in mouse male germ cells. Proc. Natl. Acad. Sci. USA 96, 6763-6768. https://doi.org/10.1073/pnas.96.12.6763
  60. Weitzer, S., and Martinez, J. (2007). The human RNA kinase hClp1 is active on 3' transfer RNA exons and short interfering RNAs. Nature 447, 222-226. https://doi.org/10.1038/nature05777
  61. Xiang, K., Tong, L., and Manley, J.L. (2014). Delineating the structural blueprint of the pre-mRNA 3'-end processing machinery. Mol. Cell. Biol. 34, 1894-1910. https://doi.org/10.1128/MCB.00084-14
  62. Xu, C., and Min, J. (2011). Structure and function of WD40 domain proteins. Protein Cell 2, 202-214. https://doi.org/10.1007/s13238-011-1018-1
  63. Yang, Q., Nausch, L.W., Martin, G., Keller, W., and Doublie, S. (2014). Crystal structure of human poly(a) polymerase gamma reveals a conserved catalytic core for canonical poly(a) polymerases. J. Mol. Biol. 426, 43-50. https://doi.org/10.1016/j.jmb.2013.09.025
  64. Yao, C., Biesinger, J., Wan, J., Weng, L., Xing, Y., Xie, X., and Shi, Y. (2012). Transcriptome-wide analyses of CstF64-RNA interactions in global regulation of mRNA alternative polyadenylation. Proc. Natl. Acad. Sci. USA 109, 18773-18778. https://doi.org/10.1073/pnas.1211101109
  65. Yao, C., Choi, E.A., Weng, L., Xie, X., Wan, J., Xing, Y., Moresco, J.J., Tu, P.G., Yates, J.R., 3rd, and Shi, Y. (2013). Overlapping and distinct functions of CstF64 and CstF64tau in mammalian mRNA 3' processing. RNA 19, 1781-1790. https://doi.org/10.1261/rna.042317.113
  66. Zhang, F., Ma, T., and Yu, X. (2013). A core hSSB1-INTS complex participates in the DNA damage response. J. Cell Sci. 126, 4850-4855. https://doi.org/10.1242/jcs.132514
  67. Zhao, W., and Manley, J.L. (1996). Complex alternative RNA processing generates an unexpected diversity of poly(A) polymerase isoforms. Mol. Cell. Biol. 16, 2378-2386. https://doi.org/10.1128/MCB.16.5.2378

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