TOR signaling regulates liquid phase separation of the SMN complex governing snRNP biogenesis
The activity of the SMN complex in promoting the assembly of pre-mRNA processing UsnRNPs correlates with condensation of the complex in nuclear Cajal bodies. While mechanistic details of its activity have been elucidated, the molecular basis for condensation remains unclear. High SMN complex phospho...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
22 June 2021
|
| In: |
Cell reports
Year: 2021, Jahrgang: 35, Heft: 12 |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2021.109277 |
| Online-Zugang: | Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.celrep.2021.109277 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S2211124721006446 
|
| Verfasserangaben: | Maximilian Schilling, Archana B. Prusty, Björn Boysen, Felix S. Oppermann, Yannick L. Riedel, Alma Husedzinovic, Homa Rasouli, Angelika König, Pradhipa Ramanathan, Jürgen Reymann, Holger Erfle, Henrik Daub, Utz Fischer, and Oliver J. Gruss |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1761083716 | ||
| 003 | DE-627 | ||
| 005 | 20220820001140.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 210623s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.celrep.2021.109277 |2 doi | |
| 035 | |a (DE-627)1761083716 | ||
| 035 | |a (DE-599)KXP1761083716 | ||
| 035 | |a (OCoLC)1341416882 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 32 |2 sdnb | ||
| 100 | 1 | |a Schilling, Maximilian Thomas |e VerfasserIn |0 (DE-588)1183412843 |0 (DE-627)1663177619 |4 aut | |
| 245 | 1 | 0 | |a TOR signaling regulates liquid phase separation of the SMN complex governing snRNP biogenesis |c Maximilian Schilling, Archana B. Prusty, Björn Boysen, Felix S. Oppermann, Yannick L. Riedel, Alma Husedzinovic, Homa Rasouli, Angelika König, Pradhipa Ramanathan, Jürgen Reymann, Holger Erfle, Henrik Daub, Utz Fischer, and Oliver J. Gruss |
| 264 | 1 | |c 22 June 2021 | |
| 300 | |a 20 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 23.06.2021 | ||
| 520 | |a The activity of the SMN complex in promoting the assembly of pre-mRNA processing UsnRNPs correlates with condensation of the complex in nuclear Cajal bodies. While mechanistic details of its activity have been elucidated, the molecular basis for condensation remains unclear. High SMN complex phosphorylation suggests extensive regulation. Here, we report on systematic siRNA-based screening for modulators of the capacity of SMN to condense in Cajal bodies and identify mTOR and ribosomal protein S6 kinase β-1 as key regulators. Proteomic analysis reveals TOR-dependent phosphorylations in SMN complex subunits. Using stably expressed or optogenetically controlled phospho mutants, we demonstrate that serine 49 and 63 phosphorylation of human SMN controls the capacity of the complex to condense in Cajal bodies via liquid-liquid phase separation. Our findings link SMN complex condensation and UsnRNP biogenesis to cellular energy levels and suggest modulation of TOR signaling as a rational concept for therapy of the SMN-linked neuromuscular disorder spinal muscular atrophy. | ||
| 650 | 4 | |a assembly of ribonucleoprotein complexes | |
| 650 | 4 | |a Cajal body | |
| 650 | 4 | |a LLPS | |
| 650 | 4 | |a mTOR | |
| 650 | 4 | |a optogenetics | |
| 650 | 4 | |a phase separation | |
| 650 | 4 | |a ribosomal protein S6-kinase β-1 (RPS6KB1) | |
| 650 | 4 | |a SMA | |
| 650 | 4 | |a SMN | |
| 650 | 4 | |a snRNP | |
| 700 | 1 | |a Prusty, Archana B. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Boysen, Björn |e VerfasserIn |0 (DE-588)1035390957 |0 (DE-627)747802181 |0 (DE-576)382972317 |4 aut | |
| 700 | 1 | |a Oppermann, Felix Sebastian |d 1978- |e VerfasserIn |0 (DE-588)144029782 |0 (DE-627)656819790 |0 (DE-576)341025224 |4 aut | |
| 700 | 1 | |a Riedel, Yannick L. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Husedzinovic, Alma |e VerfasserIn |0 (DE-588)102816940X |0 (DE-627)730406865 |0 (DE-576)375672885 |4 aut | |
| 700 | 1 | |a Rasouli, Homa |e VerfasserIn |4 aut | |
| 700 | 1 | |a König, Angelika |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ramanathan, Pradhipa |e VerfasserIn |4 aut | |
| 700 | 1 | |a Reymann, Jürgen |e VerfasserIn |0 (DE-588)134002326 |0 (DE-627)573370087 |0 (DE-576)30024729X |4 aut | |
| 700 | 1 | |a Erfle, Holger |e VerfasserIn |0 (DE-588)1033880965 |0 (DE-627)742725650 |0 (DE-576)184848008 |4 aut | |
| 700 | 1 | |a Daub, Henrik |d 1968- |e VerfasserIn |0 (DE-588)120425300 |0 (DE-627)629423024 |0 (DE-576)324165234 |4 aut | |
| 700 | 1 | |a Fischer, Utz |d 1964- |e VerfasserIn |0 (DE-588)12872577X |0 (DE-627)707054869 |0 (DE-576)216183480 |4 aut | |
| 700 | 1 | |a Gruss, Oliver |e VerfasserIn |0 (DE-588)1038251028 |0 (DE-627)757162541 |0 (DE-576)179138391 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cell reports |d Maryland Heights, MO : Cell Press, 2012 |g 35(2021), 12, Artikel-ID 109277 |h Online-Ressource |w (DE-627)684964562 |w (DE-600)2649101-1 |w (DE-576)358411572 |x 2211-1247 |7 nnas |a TOR signaling regulates liquid phase separation of the SMN complex governing snRNP biogenesis |
| 773 | 1 | 8 | |g volume:35 |g year:2021 |g number:12 |g elocationid:109277 |g extent:20 |a TOR signaling regulates liquid phase separation of the SMN complex governing snRNP biogenesis |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.celrep.2021.109277 |x Resolving-System |x Verlag |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://www.sciencedirect.com/science/article/pii/S2211124721006446 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20210623 | ||
| 993 | |a Article | ||
| 994 | |a 2021 | ||
| 998 | |g 1038251028 |a Gruss, Oliver |m 1038251028:Gruss, Oliver |d 700000 |d 706000 |e 700000PG1038251028 |e 706000PG1038251028 |k 0/700000/ |k 1/700000/706000/ |p 14 |y j | ||
| 998 | |g 1033880965 |a Erfle, Holger |m 1033880965:Erfle, Holger |d 700000 |d 716000 |e 700000PE1033880965 |e 716000PE1033880965 |k 0/700000/ |k 1/700000/716000/ |p 11 | ||
| 998 | |g 134002326 |a Reymann, Jürgen |m 134002326:Reymann, Jürgen |d 700000 |d 716000 |e 700000PR134002326 |e 716000PR134002326 |k 0/700000/ |k 1/700000/716000/ |p 10 | ||
| 998 | |g 102816940X |a Husedzinovic, Alma |m 102816940X:Husedzinovic, Alma |p 6 | ||
| 998 | |g 1035390957 |a Boysen, Björn |m 1035390957:Boysen, Björn |d 140000 |e 140000PB1035390957 |k 0/140000/ |p 3 | ||
| 999 | |a KXP-PPN1761083716 |e 3940872865 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"person":[{"role":"aut","family":"Schilling","display":"Schilling, Maximilian Thomas","given":"Maximilian Thomas"},{"family":"Prusty","role":"aut","display":"Prusty, Archana B.","given":"Archana B."},{"given":"Björn","display":"Boysen, Björn","family":"Boysen","role":"aut"},{"family":"Oppermann","role":"aut","display":"Oppermann, Felix Sebastian","given":"Felix Sebastian"},{"given":"Yannick L.","role":"aut","family":"Riedel","display":"Riedel, Yannick L."},{"role":"aut","family":"Husedzinovic","display":"Husedzinovic, Alma","given":"Alma"},{"family":"Rasouli","role":"aut","display":"Rasouli, Homa","given":"Homa"},{"given":"Angelika","family":"König","role":"aut","display":"König, Angelika"},{"given":"Pradhipa","family":"Ramanathan","role":"aut","display":"Ramanathan, Pradhipa"},{"family":"Reymann","role":"aut","display":"Reymann, Jürgen","given":"Jürgen"},{"family":"Erfle","role":"aut","display":"Erfle, Holger","given":"Holger"},{"display":"Daub, Henrik","family":"Daub","role":"aut","given":"Henrik"},{"display":"Fischer, Utz","family":"Fischer","role":"aut","given":"Utz"},{"role":"aut","family":"Gruss","display":"Gruss, Oliver","given":"Oliver"}],"language":["eng"],"note":["Gesehen am 23.06.2021"],"origin":[{"dateIssuedKey":"2021","dateIssuedDisp":"22 June 2021"}],"name":{"displayForm":["Maximilian Schilling, Archana B. Prusty, Björn Boysen, Felix S. Oppermann, Yannick L. Riedel, Alma Husedzinovic, Homa Rasouli, Angelika König, Pradhipa Ramanathan, Jürgen Reymann, Holger Erfle, Henrik Daub, Utz Fischer, and Oliver J. Gruss"]},"type":{"media":"Online-Ressource","bibl":"article-journal"},"id":{"doi":["10.1016/j.celrep.2021.109277"],"eki":["1761083716"]},"recId":"1761083716","title":[{"title_sort":"TOR signaling regulates liquid phase separation of the SMN complex governing snRNP biogenesis","title":"TOR signaling regulates liquid phase separation of the SMN complex governing snRNP biogenesis"}],"physDesc":[{"extent":"20 S."}],"relHost":[{"origin":[{"dateIssuedKey":"2012","publisherPlace":"Maryland Heights, MO ; [New York, NY]","dateIssuedDisp":"2012-","publisher":"Cell Press ; Elsevier"}],"disp":"TOR signaling regulates liquid phase separation of the SMN complex governing snRNP biogenesisCell reports","type":{"bibl":"periodical","media":"Online-Ressource"},"recId":"684964562","id":{"issn":["2211-1247"],"zdb":["2649101-1"],"eki":["684964562"]},"language":["eng"],"pubHistory":["1.2012 -"],"part":{"issue":"12","volume":"35","year":"2021","text":"35(2021), 12, Artikel-ID 109277","extent":"20"},"title":[{"title_sort":"Cell reports","title":"Cell reports"}],"physDesc":[{"extent":"Online-Ressource"}]}]} | ||
| SRT | |a SCHILLINGMTORSIGNALI2220 | ||