RNA: state memory and mediator of cellular phenotype.
It has become increasingly clear that the genome is dynamic and exquisitely sensitive, changing expression patterns in response to age, environmental stimuli and pharmacological and physiological manipulations. Similarly, cellular phenotype, traditionally viewed as a stable end-state, should be viewed as versatile and changeable. The phenotype of a cell is better defined as a 'homeostatic phenotype' implying plasticity resulting from a dynamically changing yet characteristic pattern of gene/protein expression. A stable change in phenotype is the result of the movement of a cell between different multidimensional identity spaces. Here, we describe a key driver of this transition and the stabilizer of phenotype: the relative abundances of the cellular RNAs. We argue that the quantitative state of RNA can be likened to a state memory, that when transferred between cells, alters the phenotype in a predictable manner.
Kim
Junhyong
J
Penn Genome Frontiers Institute, Department of Biology, University of Pennsylvania Medical School, University of Pennsylvania, Philadelphia, PA 19104, USA. junhyong@sas.upenn.edu
Eberwine
James
J
D000818:Animals; D002468:Cell Physiological Phenomena; D020869:Gene Expression Profiling; D006801:Humans; D010641:Phenotype; D012313:RNA / Q000378:metabolism*; D049490:Systems Biology
D012313:RNA
Cancer Cell. 2006 Mar;9(3):189-98
16530703
Science. 1964 May 1;144(3618):493-9
14197558
Curr Opin Drug Discov Devel. 2003 Mar;6(2):231-6
12669459
Nature. 2008 Sep 18;455(7211):401-5
18724358
Nat Rev Neurosci. 2002 Apr;3(4):271-80
11967557
Stem Cells. 2001;19(3):193-204
11359944
Proc Natl Acad Sci U S A. 1990 Mar;87(5):1663-7
1689846
Science. 2005 Nov 18;310(5751):1139-43
16293750
Monogr Clin Cytol. 1961;2:1-142
4950279
Cell Stem Cell. 2008 Jan 10;2(1):10-2
18371415
J Neurosci. 2001 Nov 1;21(21):8310-4
11606616
Pac Symp Biocomput. 2000;:418-29
10902190
Dev Cell. 2004 Apr;6(4):483-95
15068789
Sci China C Life Sci. 2006 Jun;49(3):201-17
16856489
Cell. 2009 Feb 6;136(3):411-9
19203577
Nat Rev Neurosci. 2004 Oct;5(10):782-92
15378038
PLoS Med. 2007 Feb;4(2):e48
17298166
Nature. 2000 Feb 3;403(6769):503-11
10676951
Proc Natl Acad Sci U S A. 2006 May 9;103(19):7304-9
16648266
Int J Dev Biol. 2005;49(2-3):201-7
15906233
Nature. 2007 Jan 11;445(7124):168-76
17151600
Bioinformatics. 2001;17 Suppl 1:S316-22
11473023
Nat Genet. 2003 Jan;33(1):49-54
12469122
Bioinformatics. 2000 Oct;16(10):906-14
11120680
Nat Biotechnol. 2008 Jan;26(1):101-6
18059259
Lancet. 2003 Aug 9;362(9382):433-9
12927430
Nat Neurosci. 2006 Jan;9(1):99-107
16369481
Proc Natl Acad Sci U S A. 2000 May 23;97(11):6144-9
10823957
Nat Genet. 2002 Dec;32 Suppl:533-40
12454650
Nat Genet. 2003 Jun;34(2):166-76
12740579
Nat Biotechnol. 2003 Nov;21(11):1337-42
14555958
Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10800-4
7971965
Nat Biotechnol. 2008 Nov;26(11):1269-75
18849973
Am J Pathol. 2001 Oct;159(4):1231-8
11583950
Cell. 2004 Mar 5;116(5):683-98
15006351
Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics. 1994 Oct;50(4):3249-3250
9962373
Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8614-9
11438714
Science. 2002 Aug 2;297(5582):836-40
12161654
Curr Opin Genet Dev. 1998 Oct;8(5):545-51
9794826
Arch Gen Psychiatry. 2002 Jul;59(7):631-40
12090816
Clin Cancer Res. 2003 Oct 15;9(13):4695-704
14581339
J Mol Biol. 2002 May 24;319(1):229-42
12051948
Cell Stem Cell. 2007 Nov;1(5):515-28
18371391
Dev Biol. 2007 Jul 15;307(2):446-59
17560561
Cell. 2006 Aug 25;126(4):677-89
16923388
Nat Med. 2002 Jan;8(1):68-74
11786909
Science. 1999 Oct 15;286(5439):509-12
10521342
Science. 2002 Mar 1;295(5560):1664-9
11872830
Annu Rev Cell Dev Biol. 2006;22:1-22
16704337
Genes Dev. 2005 May 15;19(10):1129-55
15905405
Stem Cells. 2008 Aug;26(8):1998-2005
18511599
Metab Eng. 2007 May;9(3):258-67
17292651
J Theor Biol. 2006 Oct 21;242(4):890-9
16806276
Nature. 1958 Jul 5;182(4627):64-5
13566187
Nat Rev Mol Cell Biol. 2004 Jun;5(6):471-80
15173826
Methods Mol Biol. 2006;329:449-58
16846009
J Exp Biol. 2005 Jun;208(Pt 12):2389-98
15939778
J Neurosci. 2007 Nov 7;27(45):12255-66
17989291
Cell Res. 2008 May;18(5):600-3
18414447
Proc Natl Acad Sci U S A. 2009 May 5;106(18):7624-9
19380745
Philos Trans R Soc Lond B Biol Sci. 2008 Jan 12;363(1489):9-22
17284414
Genome Biol. 2004;5(12):R100
15575966
Development. 2008 Nov;135(21):3481-9
18849528
Trends Biotechnol. 2003 Jun;21(6):255-62
12788545
Neuron. 1992 Sep;9(3):539-48
1388031