A short conserved motif in ALYREF directs cap- and EJC-dependent assembly of export complexes on spliced mRNAs

Gromadzka, Agnieszka M.; Steckelberg, Anna-Lena; Singh, Kusum; Hofmann, Kay; Gehring, Niels H.

doi:10.1093/nar/gkw009

Cited by 74 publications

(74 citation statements)

References 69 publications

(118 reference statements)

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“…RBD, RNA-binding domain; R-rich, arginine-rich; RS-rich, arginine/serine-rich; RRM, RNA recognition motif (not necessarily involved in RNA binding). UBM, UAP56 (DDX39B)-binding motif; WxHD corresponds to the recently identified motif which binds EIF4AIII [12]. The other domains are all well characterized.…”

Section: The Composition Of Trexmentioning

confidence: 99%

The role of TREX in gene expression and disease

Heath

Viphakone

Wilson

2016

Biochemical Journal

167

186

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TRanscription and EXport (TREX) is a conserved multisubunit complex essential for embryogenesis, organogenesis and cellular differentiation throughout life. By linking transcription, mRNA processing and export together, it exerts a physiologically vital role in the gene expression pathway. In addition, this complex prevents DNA damage and regulates the cell cycle by ensuring optimal gene expression. As the extent of TREX activity in viral infections, amyotrophic lateral sclerosis and cancer emerges, the need for a greater understanding of TREX function becomes evident. A complete elucidation of the composition, function and interactions of the complex will provide the framework for understanding the molecular basis for a variety of diseases. This review details the known composition of TREX, how it is regulated and its cellular functions with an emphasis on mammalian systems.

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Section: The Composition Of Trexmentioning

confidence: 99%

The role of TREX in gene expression and disease

Heath

Viphakone

Wilson

2016

Biochemical Journal

167

186

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“…WxHD was identified to play a role in the subnuclear localisation of mammalian ALY 246 (Gromadzka et al 2016). Since this motif also occurs in ALY1 and a similar WxxD motif is 247 found in ALY2, but not in ALY3 and ALY4 (Supplemental Fig.…”

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confidence: 97%

ALY RNA-Binding Proteins Are Required for Nucleocytosolic mRNA Transport and Modulate Plant Growth and Development

et al. 2018

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3 ABSTRACT 49The regulated transport of mRNAs from the cell nucleus to the cytosol is a critical step 50 linking transcript synthesis and processing with translation. However, in plants, only few of 51 the factors that act in the mRNA export pathway have been functionally characterised. 52Flowering plant genomes encode several members of the ALY protein family, which function 53 as mRNA export factors in other organisms. Arabidopsis thaliana ALY1-4 are commonly 54 detected in root and leaf cells, but are differentially expressed in reproductive tissue. 55Moreover, the subnuclear distribution of ALY1/2 differs from that of ALY3/4. ALY1 binds 56 with higher affinity to ssRNA than dsRNA and ssDNA, and interacts preferentially with 5- THO rather than that of yeast (Yelina et al. 2010). Likewise, THO associates with UAP56, 99ALYs and MOS11 (the orthologue of CIP29) in Arabidopsis cells (Sørensen et al. 2017 (Germain et al. 2010;Lu et al. 2010;Pan et al. 2012;Xu et al. 2015; 114 Sørensen et al. 2017), but so far none of the ALY mRNA export adaptor candidates have been 115shown to function in nucleo-cytosolic transport of mRNAs in plants. 116In this study, we have systematically studied the Arabidopsis ALY proteins including their RESULTS 126 ALY proteins in Arabidopsis and other plants 127First, we compared the amino acid sequences of the four Arabidopsis ALY proteins (ALY1- sequence identity) as well as ALY3 and ALY4 (70% amino acid sequence identity) share a 137 high degree of sequence similarity, whereas the similarity of ALY1/2 versus ALY3/4 is 138 clearly lower (<42% amino acid sequence identity) (Supplemental Fig. S1B (Fig. 1A). ALY1 and truncated versions of the protein were expressed in 157 E. coli as 6xHis-GB1 fusion proteins, purified by two-step chromatography, and examined by 158 SDS-PAGE (Fig. 1B). For comparison we also used the unfused 6xHis-GB1 tag. The purified (Fig. 1C, Student's t-test, P < 0.05 and P < 0.001, respectively). The unfused 6xHis-GB1 165 tag did not exhibit affinity for ssRNA. To examine which domains of ALY1 contribute to the 166 RNA interactions, the binding to ssRNA of the different recombinant ALY1 versions was 167 measured (Fig. 1D (Fig. 3C, D). Therefore, the four ALY proteins and UAP56 228 are widely expressed in sporophytic cells of Arabidopsis plants. 229The subnuclear localisation of the ALY-GFP fusions was inspected in more detail by 230 CLSM in comparison to the UAP56-GFP and GFP-NLS controls. GFP-NLS (Antosch et al. immunofluorescence microscopy analysis (Kammel et al. 2013 (Table S1). In leaf cells, the nucleoplasmic distribution of 238 the ALY proteins appeared more heterogeneous than in root cells particularly for ALY4 that 239 partially localised to nucleoplasmic foci (Fig. 4B). Notably, the nucleolar enrichment of 253In view of the apparently ubiquitous expression of the four ALY-GFP proteins in 254 sporophytic cells, their occurrence was analysed in male and female gametophytes by CLSM. 255In mature pollen grains (Fig. 5A), the fluorescent signal of ALY1-...

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“…The assembly of nuclear export-competent messenger ribonucleoprotein complexes comprises the recruitment of export-facilitating factors to the mature mRNA. It was shown lately that a core set of export proteins containing UAP56, DDX and importantly, ALYREF, nucleate and associate with spliced transcripts in an EJC-and cap-dependent manner [11]. Further studies are needed to explore the hypothesis that EJC and ALYREF play a major role in both m …”

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confidence: 99%