title: Hierarchical regulation of mRNA partitioning between the cytoplasm and the endoplasmic reticulum of mammalian cells.
abstract: The mRNA transcriptome is currently thought to be partitioned between the cytosol and endoplasmic reticulum (ER) compartments by binary selection; mRNAs encoding cytosolic/nucleoplasmic proteins are translated on free ribosomes, and mRNAs encoding topogenic signal-bearing proteins are translated on ER-bound ribosomes, with ER localization being conferred by the signal-recognition particle pathway. In subgenomic and genomic analyses of subcellular mRNA partitioning, we report an overlapping subcellular distribution of cytosolic/nucleoplasmic and topogenic signal-encoding mRNAs, with mRNAs of both cohorts displaying noncanonical subcellular partitioning patterns. Unexpectedly, the topogenic signal-encoding mRNA transcriptome was observed to partition in a hierarchical, cohort-specific manner. mRNAs encoding resident proteins of the endomembrane system were clustered at high ER-enrichment values, whereas mRNAs encoding secretory pathway cargo were broadly represented on free and ER-bound ribosomes. Two distinct modes of mRNA association with the ER were identified. mRNAs encoding endomembrane-resident proteins were bound via direct, ribosome-independent interactions, whereas mRNAs encoding secretory cargo displayed predominantly ribosome-dependent modes of ER association. These data indicate that mRNAs are partitioned between the cytosol and ER compartments via a hierarchical system of intrinsic and encoded topogenic signals and identify mRNA cohort-restricted modes of mRNA association with the ER.
authors: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors: Qiang
authors: Q
authors: Chen
authors: Sujatha
authors: S
authors: Jagannathan
authors: David W
authors: DW
authors: Reid
authors: Tianli
authors: T
authors: Zheng
authors: Christopher V
authors: CV
authors: Nicchitta
references: J Biol Chem. 2002 Jun 28;277(26):23314-20
references: 11964406
references: RNA. 2008 Mar;14(3):445-53
references: 18192611
references: J Mol Biol. 2004 Jul 16;340(4):783-95
references: 15223320
references: J Mol Biol. 1971 Jul 28;59(2):243-53
references: 4998472
references: DNA Res. 2009 Feb;16(1):45-58
references: 19001483
references: Methods Enzymol. 2007;431:47-60
references: 17923230
references: PLoS Genet. 2006 Jan;2(1):e11
references: 16415983
references: J Cell Biol. 1989 Dec;109(6 Pt 2):3223-30
references: 2557350
references: J Mol Biol. 2001 Jan 19;305(3):567-80
references: 11152613
references: Curr Opin Cell Biol. 2002 Aug;14(4):412-6
references: 12383790
references: Nat Rev Mol Cell Biol. 2007 Jun;8(6):429-39
references: 17505521
references: J Mol Biol. 1966 Aug;19(2):503-24
references: 4961331
references: J Cell Biol. 1975 Jun;65(3):513-28
references: 1133114
references: Biochem Biophys Res Commun. 1980 Mar 28;93(2):521-7
references: 7387657
references: Plant J. 2006 May;46(4):708-21
references: 16640606
references: J Cell Biol. 1981 Jan;88(1):29-36
references: 6782109
references: Mol Biol Cell. 2002 Nov;13(11):3775-86
references: 12429823
references: J Biol Chem. 2001 Jul 13;276(28):26132-40
references: 11359769
references: Trends Biochem Sci. 2006 Oct;31(10):563-71
references: 16919958
references: Biochem Cell Biol. 2005 Dec;83(6):687-95
references: 16333319
references: Recent Prog Horm Res. 1980;36:451-75
references: 6997945
references: Cell. 1979 Feb;16(2):303-12
references: 455437
references: Mol Biol Cell. 2001 Mar;12(3):577-88
references: 11251072
references: Cell. 1991 Oct 4;67(1):131-44
references: 1655273
references: J Cell Biol. 1973 Jan;56(1):206-29
references: 4682341
references: Methods Enzymol. 2009;463:619-29
references: 19892195
references: Chembiochem. 2000 Aug 18;1(2):86-102
references: 11828402
references: J Cell Biol. 1981 Nov;91(2 Pt 1):557-61
references: 7309797
references: Proc Natl Acad Sci U S A. 1980 Mar;77(3):1496-500
references: 6929499
references: Cell. 2007 Oct 5;131(1):174-87
references: 17923096
references: Curr Opin Cell Biol. 2009 Jun;21(3):409-15
references: 19249199
references: J Cell Biol. 1981 Nov;91(2 Pt 1):545-50
references: 7309795
references: Dev Cell. 2002 Feb;2(2):207-17
references: 11832246
references: J Cell Biol. 1977 Aug;74(2):414-27
references: 885910
references: Cell. 2008 May 2;133(3):440-51
references: 18455985
references: Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9973-8
references: 9707585
references: J Cell Biol. 1981 Nov;91(2 Pt 1):551-6
references: 7309796
references: J Cell Biol. 1981 Aug;90(2):495-506
references: 6116718
references: Cell. 1996 Feb 9;84(3):395-400
references: 8608593
references: RNA. 2003 Sep;9(9):1123-37
references: 12923260
references: J Cell Biol. 1975 Dec;67(3):835-51
references: 811671
references: J Biol Chem. 2000 Oct 27;275(43):33828-35
references: 10924518
references: Nature. 2009 Feb 5;457(7230):736-40
references: 19079237
references: Methods Mol Biol. 2008;419:197-214
references: 18369985
references: Annu Rev Cell Biol. 1994;10:87-119
references: 7888184
references: Mol Biol Cell. 2005 Dec;16(12):5819-31
references: 16221886
references: Mol Biol Cell. 2008 Feb;19(2):623-32
references: 18077556
references: J Cell Biol. 1976 Oct;71(1):307-13
references: 824293
references: J Lipid Res. 1992 Sep;33(9):1255-67
references: 1402395
references: Nat Genet. 2000 May;25(1):58-62
references: 10802657
references: Symp Soc Exp Biol. 1979;33:9-36
references: 524275
references: Dev Cell. 2005 Oct;9(4):545-54
references: 16198296
references: Trends Cell Biol. 2001 Mar;11(3):112-5
references: 11306271
references: J Mol Biol. 1971 Jul 28;59(2):227-41
references: 4998471
references: J Cell Biol. 2001 Oct 15;155(2):181-5
references: 11604416
references: Science. 2011 Feb 4;331(6017):586-9
references: 21233347
references: FASEB J. 1991 Mar 1;5(3):301-8
references: 2001789
references: J Mol Biol. 1974 Oct 25;89(2):327-38
references: 4216643
references: Mol Biol Cell. 2004 Nov;15(11):5064-74
references: 15356269
references: J Cell Biol. 1975 Dec;67(3):852-62
references: 811672