scholarly journals Biogenesis of the Signal Recognition Particle (Srp) Involves Import of Srp Proteins into the Nucleolus, Assembly with the Srp-Rna, and Xpo1p-Mediated Export

2001 ◽  
Vol 153 (4) ◽  
pp. 745-762 ◽  
Author(s):  
Helge Grosshans ◽  
Karina Deinert ◽  
Ed Hurt ◽  
George Simos
Keyword(s):  
Nuclear Export ◽  
Protein Import ◽  
Signal Recognition Particle ◽  
Nuclear Export Signal ◽  
Secretory Proteins ◽  
Signal Recognition ◽  
Core Proteins ◽  
Import Receptors ◽  
Export Signal ◽  
Srp Rna

The signal recognition particle (SRP) targets nascent secretory proteins to the ER, but how and where the SRP assembles is largely unknown. Here we analyze the biogenesis of yeast SRP, which consists of an RNA molecule (scR1) and six proteins, by localizing all its components. Although scR1 is cytoplasmic in wild-type cells, nuclear localization was observed in cells lacking any one of the four SRP “core proteins” Srp14p, Srp21p, Srp68p, or Srp72p. Consistently, a major nucleolar pool was detected for these proteins. Sec65p, on the other hand, was found in both the nucleoplasm and the nucleolus, whereas Srp54p was predominantly cytoplasmic. Import of the core proteins into the nucleolus requires the ribosomal protein import receptors Pse1p and Kap123p/Yrb4p, which might, thus, constitute a nucleolar import pathway. Nuclear export of scR1 is mediated by the nuclear export signal receptor Xpo1p, is distinct from mRNA transport, and requires, as evidenced by the nucleolar accumulation of scR1 in a dis3/rrp44 exosome component mutant, an intact scR1 3′ end. A subset of nucleoporins, including Nsp1p and Nup159p (Rat7p), are also necessary for efficient translocation of scR1 from the nucleus to the cytoplasm. We propose that assembly of the SRP requires import of all SRP core proteins into the nucleolus, where they assemble into a pre-SRP with scR1. This particle can then be targeted to the nuclear pores and is subsequently exported to the cytoplasm in an Xpo1p-dependent way.

scholarly journals Altered Nuclear Export Signal Recognition as a Driver of Oncogenesis

2019 ◽  
Vol 9 (10) ◽  
pp. 1452-1467 ◽  
Author(s):  
Justin Taylor ◽  
Maria Sendino ◽  
Alexander N. Gorelick ◽  
Alessandro Pastore ◽  
Matthew T. Chang ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Nuclear Export Signal ◽  
Signal Recognition ◽  
Export Signal

scholarly journals Structural basis for leucine-rich nuclear export signal recognition by CRM1

Nature ◽  
2009 ◽  
Vol 458 (7242) ◽  
pp. 1136-1141 ◽  
Author(s):  
Xiuhua Dong ◽  
Anindita Biswas ◽  
Katherine E. Süel ◽  
Laurie K. Jackson ◽  
Rita Martinez ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Nuclear Export Signal ◽  
Structural Basis ◽  
Signal Recognition ◽  
Export Signal

Assembly of the Alu domain of the signal recognition particle (SRP): dimerization of the two protein components is required for efficient binding to SRP RNA

1990 ◽  
Vol 10 (2) ◽  
pp. 777-784
Author(s):  
K Strub ◽  
P Walter
Keyword(s):  
Cdna Clone ◽  
Repetitive Sequences ◽  
Signal Recognition Particle ◽  
Secretory Proteins ◽  
Endoplasmic Reticulum Membrane ◽  
Cdna Clones ◽  
Functional Domain ◽  
Signal Recognition ◽  
Srp Rna

The signal recognition particle (SRP), a cytoplasmic ribonucleoprotein, plays an essential role in targeting secretory proteins to the rough endoplasmic reticulum membrane. In addition to the targeting function, SRP contains an elongation arrest or pausing function. This function is carried out by the Alu domain, which consists of two proteins, SRP9 and SRP14, and the portion of SRP (7SL) RNA which is homologous to the Alu family of repetitive sequences. To study the assembly pathway of the components in the Alu domain, we have isolated a cDNA clone of SRP9, in addition to a previously obtained cDNA clone of SRP14. We show that neither SRP9 nor SRP14 alone interacts specifically with SRP RNA. Rather, the presence of both proteins is required for the formation of a stable RNA-protein complex. Furthermore, heterodimerization of SRP9 and SRP14 occurs in the absence of SRP RNA. Since a partially reconstituted SRP lacking SRP9 and SRP14 [SRP(-9/14)] is deficient in the elongation arrest function, it follows from our results that both proteins are required to assemble a functional domain. In addition, SRP9 and SRP14 synthesized in vitro from synthetic mRNAs derived from their cDNA clones restore elongation arrest activity to SRP(-9/14).

Structural insights into the assembly of the human and archaeal signal recognition particles

2010 ◽  
Vol 66 (3) ◽  
pp. 295-303 ◽  
Author(s):  
Klemens Wild ◽  
Gert Bange ◽  
Gunes Bozkurt ◽  
Bernd Segnitz ◽  
Astrid Hendricks ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Rna Structure ◽  
Signal Recognition Particle ◽  
Secretory Proteins ◽  
Signal Recognition ◽  
Induced Fit ◽  
Binary Complexes ◽  
Rnp Complex ◽  
Structural Insights ◽  
Srp Rna

The signal recognition particle (SRP) is a conserved ribonucleoprotein (RNP) complex that co-translationally targets membrane and secretory proteins to membranes. The assembly of the particle depends on the proper folding of the SRP RNA, which in mammalia and archaea involves an induced-fit mechanism within helices 6 and 8 in the S domain of SRP. The two helices are juxtaposed and clamped together upon binding of the SRP19 protein to their apices. In the current assembly paradigm, archaeal SRP19 causes the asymmetric loop of helix 8 to bulge out and expose the binding platform for the key player SRP54. Based on a heterologous archaeal SRP19–human SRP RNA structure, mammalian SRP19 was thought not to be able to induce this change, thus explaining the different requirements of SRP19 for SRP54 recruitment. In contrast, the crystal structures of a crenarchaeal and the all-human SRP19–SRP RNA binary complexes presented here show that the asymmetric loop is bulged out in both binary complexes. Differences in SRP assembly between mammalia and archaea are therefore independent of SRP19 and are based on differences in SRP RNA itself. A new SRP-assembly scheme is presented.

scholarly journals A nuclear export signal is essential for the cytosolic localization of the Ran binding protein, RanBP1.

1996 ◽  
Vol 134 (5) ◽  
pp. 1157-1168 ◽  
Author(s):  
S A Richards ◽  
K M Lounsbury ◽  
K L Carey ◽  
I G Macara
Keyword(s):  
Nuclear Export ◽  
Protein Import ◽  
Nuclear Protein ◽  
Fluorescent Protein ◽  
Binding Protein ◽  
Nuclear Export Signal ◽  
Cyclin B1 ◽  
Nuclear Accumulation ◽  
Protein Fusion ◽  
Export Signal

RanBP1 is a Ran/TC4 binding protein that can promote the interaction between Ran and beta-importin /beta-karyopherin, a component of the docking complex for nuclear protein cargo. This interaction occurs through a Ran binding domain (RBD). Here we show that RanBP1 is primarily cytoplasmic, but the isolated RBD accumulates in the nucleus. A region COOH-terminal to the RBD is responsible for this cytoplasmic localization. This domain acts heterologously, localizing a nuclear cyclin B1 mutant to the cytoplasm. The domain contains a nuclear export signal that is necessary but not sufficient for the nuclear export of a functional RBD In transiently transfected cells, epitope-tagged RanBP1 promotes dexamethasone-dependent nuclear accumulation of a glucocorticoid receptor-green fluorescent protein fusion, but the isolated RBD potently inhibits this accumulation. The cytosolic location of RanBP1 may therefore be important for nuclear protein import. RanBP1 may provide a key link between the nuclear import and export pathways.

scholarly journals Erratum: Structural basis for leucine-rich nuclear export signal recognition by CRM1

Nature ◽  
2009 ◽  
Vol 461 (7263) ◽  
pp. 550-550
Author(s):  
Xiuhua Dong ◽  
Anindita Biswas ◽  
Katherine E. Süel ◽  
Laurie K. Jackson ◽  
Rita Martinez ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Nuclear Export Signal ◽  
Structural Basis ◽  
Signal Recognition ◽  
Export Signal

scholarly journals Assembly of the Alu domain of the signal recognition particle (SRP): dimerization of the two protein components is required for efficient binding to SRP RNA.

1990 ◽  
Vol 10 (2) ◽  
pp. 777-784 ◽  
Author(s):  
K Strub ◽  
P Walter
Keyword(s):  
Cdna Clone ◽  
Repetitive Sequences ◽  
Signal Recognition Particle ◽  
Secretory Proteins ◽  
Endoplasmic Reticulum Membrane ◽  
Cdna Clones ◽  
Functional Domain ◽  
Signal Recognition ◽  
Srp Rna

The signal recognition particle (SRP), a cytoplasmic ribonucleoprotein, plays an essential role in targeting secretory proteins to the rough endoplasmic reticulum membrane. In addition to the targeting function, SRP contains an elongation arrest or pausing function. This function is carried out by the Alu domain, which consists of two proteins, SRP9 and SRP14, and the portion of SRP (7SL) RNA which is homologous to the Alu family of repetitive sequences. To study the assembly pathway of the components in the Alu domain, we have isolated a cDNA clone of SRP9, in addition to a previously obtained cDNA clone of SRP14. We show that neither SRP9 nor SRP14 alone interacts specifically with SRP RNA. Rather, the presence of both proteins is required for the formation of a stable RNA-protein complex. Furthermore, heterodimerization of SRP9 and SRP14 occurs in the absence of SRP RNA. Since a partially reconstituted SRP lacking SRP9 and SRP14 [SRP(-9/14)] is deficient in the elongation arrest function, it follows from our results that both proteins are required to assemble a functional domain. In addition, SRP9 and SRP14 synthesized in vitro from synthetic mRNAs derived from their cDNA clones restore elongation arrest activity to SRP(-9/14).

Nuclear export of signal recognition particle RNA is a facilitated process that involves the Alu sequence domain

1994 ◽  
Vol 107 (4) ◽  
pp. 903-912 ◽  
Author(s):  
X.P. He ◽  
N. Bataille ◽  
H.M. Fried
Keyword(s):  
Nuclear Export ◽  
Signal Recognition Particle ◽  
Nuclear Pore ◽  
Dependent Manner ◽  
Signal Recognition ◽  
Cytoplasmic Rna ◽  
Alu Sequence ◽  
Alu Element ◽  
Sequence Domain ◽  
Srp Rna

The signal recognition particle is a cytoplasmic RNA-protein complex that mediates translocation of secretory polypeptides into the endoplasmic reticulum. We have used a Xenopus oocyte microinjection assay to determine how signal recognition particle (SRP) RNA is exported from the nucleus. Following nuclear injection, SRP RNA accumulated in the cytoplasm while cytoplasmically injected SRP RNA did not enter the nucleus. Cytoplasmic accumulation of SRP RNA was an apparently facilitated process dependent on limiting trans-acting factors, since nuclear export exhibited saturation kinetics and was completely blocked either at low temperature or by wheat germ agglutinin, a known inhibitor of nuclear pore-mediated transport. At least one target for trans-acting factors that promote nuclear export of SRP RNA appears to be the Alu element of the molecule, since a transcript consisting of only the Alu sequence was exported from the nucleus in a temperature-dependent manner and the Alu transcript competed in the nucleus for transport with intact SRP RNA. Although the identities of trans-acting factors responsible for SRP RNA transport are at present unknown, we suggest that proteins contained within the cytoplasmic form of SRP are candidates. Consistent with this idea were the effects of a mutation in SRP RNA that prevented binding of two known SRP proteins to the Alu sequence.

The Structure of BRMS1 Nuclear Export Signal and SNX6 Interacting Region Reveals a Hexamer Formed by Antiparallel Coiled Coils

2011 ◽  
Vol 411 (5) ◽  
pp. 1114-1127 ◽  
Author(s):  
Mercedes Spínola-Amilibia ◽  
José Rivera ◽  
Miguel Ortiz-Lombardía ◽  
Antonio Romero ◽  
José L. Neira ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Nuclear Export Signal ◽  
Coiled Coils ◽  
Export Signal
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