Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses

Katannya Kapeli; Gabriel A. Pratt; Anthony Q. Vu; Kasey R. Hutt; Fernando J. Martinez; Balaji Sundararaman; Ranjan Batra; Peter Freese; Nicole J. Lambert; Stephanie C. Huelga; Seung J. Chun; Tiffany Y. Liang; Jeremy Chang; John P. Donohue; Lily Shiue; Jiayu Zhang; Haining Zhu; Franca Cambi; Edward Kasarskis; Shawn Hoon; Manuel Ares; Christopher B. Burge; John Ravits; Frank Rigo; Gene W. Yeo

doi:10.1038/ncomms12143

Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses

Katannya Kapeli
, Gabriel A. Pratt
, Anthony Q. Vu
, Kasey R. Hutt
, Fernando J. Martinez
, Balaji Sundararaman
, Ranjan Batra
, Peter Freese
, Nicole J. Lambert
, Stephanie C. Huelga
, Seung J. Chun
, Tiffany Y. Liang
, Jeremy Chang
, John P. Donohue
, Lily Shiue
, Jiayu Zhang
, Haining Zhu
, Franca Cambi
, Edward Kasarskis
, Shawn Hoon

Manuel Ares, Christopher B. Burge, John Ravits, Frank Rigo, Gene W. Yeo

Producción científica: Article › revisión exhaustiva

142 Citas (Scopus)

Resumen

The RNA-binding protein (RBP) TAF15 is implicated in amyotrophic lateral sclerosis (ALS). To compare TAF15 function to that of two ALS-associated RBPs, FUS and TDP-43, we integrate CLIP-seq and RNA Bind-N-Seq technologies, and show that TAF15 binds to ∼4,900 RNAs enriched for GGUA motifs in adult mouse brains. TAF15 and FUS exhibit similar binding patterns in introns, are enriched in 3′ untranslated regions and alter genes distinct from TDP-43. However, unlike FUS and TDP-43, TAF15 has a minimal role in alternative splicing. In human neural progenitors, TAF15 and FUS affect turnover of their RNA targets. In human stem cell-derived motor neurons, the RNA profile associated with concomitant loss of both TAF15 and FUS resembles that observed in the presence of the ALS-associated mutation FUS R521G, but contrasts with late-stage sporadic ALS patients. Taken together, our findings reveal convergent and divergent roles for FUS, TAF15 and TDP-43 in RNA metabolism.

Idioma original	English
Número de artículo	12143
Publicación	Nature Communications
Volumen	7
DOI	https://doi.org/10.1038/ncomms12143
Estado	Published - jul 5 2016

Nota bibliográfica

Funding Information:
S.C.H. and G.A.P. were funded by National Science Foundation Graduate Research Fellowships. G.A.P. was also partially supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number T32GM008666. This work was supported by grants from the National Institutes of Health (HG004659, NS075449 and HG007005 to G.W.Y; NS077284 to H.Z.), the California Institute of Regenerative Medicine (RB3-05009 and RB4-06045 to G.W.Y.) and ALS Association (VC8K27 to G.W.Y.; 6SE340 to H.Z.). This work was partially supported by NIH grant HG007005 to C.B.B.

Financiación

S.C.H. and G.A.P. were funded by National Science Foundation Graduate Research Fellowships. G.A.P. was also partially supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number T32GM008666. This work was supported by grants from the National Institutes of Health (HG004659, NS075449 and HG007005 to G.W.Y; NS077284 to H.Z.), the California Institute of Regenerative Medicine (RB3-05009 and RB4-06045 to G.W.Y.) and ALS Association (VC8K27 to G.W.Y.; 6SE340 to H.Z.). This work was partially supported by NIH grant HG007005 to C.B.B.

Financiadores	Número del financiador
National Science Foundation Arctic Social Science Program
National Institutes of Health (NIH)	HG004659, HG007005, NS077284
National Institute of General Medical Sciences DP2GM119177 Sophie Dumont National Institute of General Medical Sciences	T32GM008666
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council	R01NS075449
American Amyotrophic Lateral Sclerosis Association	6SE340, VC8K27
California Institute for Regenerative Medicine	RB3-05009, RB4-06045

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

Acceder al documento

10.1038/ncomms12143

Otros archivos y enlaces

Link to publication in Scopus

Citar esto

Kapeli, K., Pratt, G. A., Vu, A. Q., Hutt, K. R., Martinez, F. J., Sundararaman, B., Batra, R., Freese, P., Lambert, N. J., Huelga, S. C., Chun, S. J., Liang, T. Y., Chang, J., Donohue, J. P., Shiue, L., Zhang, J., Zhu, H., Cambi, F., Kasarskis, E., ... Yeo, G. W. (2016). Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses. Nature Communications, 7, Artículo 12143. https://doi.org/10.1038/ncomms12143

@article{7e378184fa904eed8f16827dc6bc164a,

title = "Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses",

abstract = "The RNA-binding protein (RBP) TAF15 is implicated in amyotrophic lateral sclerosis (ALS). To compare TAF15 function to that of two ALS-associated RBPs, FUS and TDP-43, we integrate CLIP-seq and RNA Bind-N-Seq technologies, and show that TAF15 binds to ∼4,900 RNAs enriched for GGUA motifs in adult mouse brains. TAF15 and FUS exhibit similar binding patterns in introns, are enriched in 3′ untranslated regions and alter genes distinct from TDP-43. However, unlike FUS and TDP-43, TAF15 has a minimal role in alternative splicing. In human neural progenitors, TAF15 and FUS affect turnover of their RNA targets. In human stem cell-derived motor neurons, the RNA profile associated with concomitant loss of both TAF15 and FUS resembles that observed in the presence of the ALS-associated mutation FUS R521G, but contrasts with late-stage sporadic ALS patients. Taken together, our findings reveal convergent and divergent roles for FUS, TAF15 and TDP-43 in RNA metabolism.",

author = "Katannya Kapeli and Pratt, \{Gabriel A.\} and Vu, \{Anthony Q.\} and Hutt, \{Kasey R.\} and Martinez, \{Fernando J.\} and Balaji Sundararaman and Ranjan Batra and Peter Freese and Lambert, \{Nicole J.\} and Huelga, \{Stephanie C.\} and Chun, \{Seung J.\} and Liang, \{Tiffany Y.\} and Jeremy Chang and Donohue, \{John P.\} and Lily Shiue and Jiayu Zhang and Haining Zhu and Franca Cambi and Edward Kasarskis and Shawn Hoon and Manuel Ares and Burge, \{Christopher B.\} and John Ravits and Frank Rigo and Yeo, \{Gene W.\}",

note = "Funding Information: S.C.H. and G.A.P. were funded by National Science Foundation Graduate Research Fellowships. G.A.P. was also partially supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number T32GM008666. This work was supported by grants from the National Institutes of Health (HG004659, NS075449 and HG007005 to G.W.Y; NS077284 to H.Z.), the California Institute of Regenerative Medicine (RB3-05009 and RB4-06045 to G.W.Y.) and ALS Association (VC8K27 to G.W.Y.; 6SE340 to H.Z.). This work was partially supported by NIH grant HG007005 to C.B.B.",

year = "2016",

month = jul,

day = "5",

doi = "10.1038/ncomms12143",

language = "English",

volume = "7",

}

Kapeli, K, Pratt, GA, Vu, AQ, Hutt, KR, Martinez, FJ, Sundararaman, B, Batra, R, Freese, P, Lambert, NJ, Huelga, SC, Chun, SJ, Liang, TY, Chang, J, Donohue, JP, Shiue, L, Zhang, J, Zhu, H, Cambi, F, Kasarskis, E, Hoon, S, Ares, M, Burge, CB, Ravits, J, Rigo, F & Yeo, GW 2016, 'Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses', Nature Communications, vol. 7, 12143. https://doi.org/10.1038/ncomms12143

TY - JOUR

T1 - Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses

AU - Kapeli, Katannya

AU - Pratt, Gabriel A.

AU - Vu, Anthony Q.

AU - Hutt, Kasey R.

AU - Martinez, Fernando J.

AU - Sundararaman, Balaji

AU - Batra, Ranjan

AU - Freese, Peter

AU - Lambert, Nicole J.

AU - Huelga, Stephanie C.

AU - Chun, Seung J.

AU - Liang, Tiffany Y.

AU - Chang, Jeremy

AU - Donohue, John P.

AU - Shiue, Lily

AU - Zhang, Jiayu

AU - Zhu, Haining

AU - Cambi, Franca

AU - Kasarskis, Edward

AU - Hoon, Shawn

AU - Ares, Manuel

AU - Burge, Christopher B.

AU - Ravits, John

AU - Rigo, Frank

AU - Yeo, Gene W.

N1 - Funding Information: S.C.H. and G.A.P. were funded by National Science Foundation Graduate Research Fellowships. G.A.P. was also partially supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number T32GM008666. This work was supported by grants from the National Institutes of Health (HG004659, NS075449 and HG007005 to G.W.Y; NS077284 to H.Z.), the California Institute of Regenerative Medicine (RB3-05009 and RB4-06045 to G.W.Y.) and ALS Association (VC8K27 to G.W.Y.; 6SE340 to H.Z.). This work was partially supported by NIH grant HG007005 to C.B.B.

PY - 2016/7/5

Y1 - 2016/7/5

N2 - The RNA-binding protein (RBP) TAF15 is implicated in amyotrophic lateral sclerosis (ALS). To compare TAF15 function to that of two ALS-associated RBPs, FUS and TDP-43, we integrate CLIP-seq and RNA Bind-N-Seq technologies, and show that TAF15 binds to ∼4,900 RNAs enriched for GGUA motifs in adult mouse brains. TAF15 and FUS exhibit similar binding patterns in introns, are enriched in 3′ untranslated regions and alter genes distinct from TDP-43. However, unlike FUS and TDP-43, TAF15 has a minimal role in alternative splicing. In human neural progenitors, TAF15 and FUS affect turnover of their RNA targets. In human stem cell-derived motor neurons, the RNA profile associated with concomitant loss of both TAF15 and FUS resembles that observed in the presence of the ALS-associated mutation FUS R521G, but contrasts with late-stage sporadic ALS patients. Taken together, our findings reveal convergent and divergent roles for FUS, TAF15 and TDP-43 in RNA metabolism.

AB - The RNA-binding protein (RBP) TAF15 is implicated in amyotrophic lateral sclerosis (ALS). To compare TAF15 function to that of two ALS-associated RBPs, FUS and TDP-43, we integrate CLIP-seq and RNA Bind-N-Seq technologies, and show that TAF15 binds to ∼4,900 RNAs enriched for GGUA motifs in adult mouse brains. TAF15 and FUS exhibit similar binding patterns in introns, are enriched in 3′ untranslated regions and alter genes distinct from TDP-43. However, unlike FUS and TDP-43, TAF15 has a minimal role in alternative splicing. In human neural progenitors, TAF15 and FUS affect turnover of their RNA targets. In human stem cell-derived motor neurons, the RNA profile associated with concomitant loss of both TAF15 and FUS resembles that observed in the presence of the ALS-associated mutation FUS R521G, but contrasts with late-stage sporadic ALS patients. Taken together, our findings reveal convergent and divergent roles for FUS, TAF15 and TDP-43 in RNA metabolism.

UR - https://www.scopus.com/pages/publications/84977518489

UR - https://www.scopus.com/pages/publications/84977518489#tab=citedBy

U2 - 10.1038/ncomms12143

DO - 10.1038/ncomms12143

M3 - Article

C2 - 27378374

AN - SCOPUS:84977518489

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 12143

ER -

Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses

Resumen

Nota bibliográfica

Financiación

ASJC Scopus subject areas

Acceder al documento

Otros archivos y enlaces

Huella

Citar esto