ELAV-like protein 1

<h2 id="structure">Structure</h2>
Of the RNA-binding ELAV/Hu family of proteins in mammals, HuR is the only <a href="/facts/Ubiquitously/TU9JYsuY">ubiquitously</a> expressed one, whereas the other three are primarily found in neuronal tissue.<a class="footnote-ref" id="fnref:5" href="#fn:5">5</a> Having a well-<a href="/facts/Conserved_sequence/YAxy2Xa2">conserved</a> primary structure to its family members, HuR has two adjacent RNA recognition motifs (RRMs) proximal to the <a href="/facts/N-terminus/yKYpuaBJ">N-terminus</a>, followed by a flexible hinge region next to a final RRM at the <a href="/facts/C-terminus/ws4scHgT">C-terminus</a>.<a class="footnote-ref" id="fnref:6" href="#fn:6">6</a> The RRM domains of HuR each contain two alpha helices with several antiparallel beta sheets in their <a href="/facts/Protein_secondary_structure/MMgXXbQ2">secondary structure</a>, a 20 amino-acid long N-terminus before RRM1 and RRM2, and a 12 amino acid linker connecting them.<a class="footnote-ref" id="fnref:7" href="#fn:7">7</a><a class="footnote-ref" id="fnref:8" href="#fn:8">8</a> The hinge region connecting RRM1,2 to RRM3 is 60 amino acids long.<a class="footnote-ref" id="fnref:9" href="#fn:9">9</a>

<h3>RNA Binding</h3>
The RRM1 domain appears to be the principal RNA-binding portion with RRM2 contributing some more contacts.<a class="footnote-ref" id="fnref:10" href="#fn:10">10</a> According to crystal structure studies, RRM1,2 domains correspond to a "moderately specific" predicted <a href="/facts/Consensus_sequence/StFdcuTb">consensus sequence</a>.<a class="footnote-ref" id="fnref:11" href="#fn:11">11</a><a class="footnote-ref" id="fnref:12" href="#fn:12">12</a> Additionally, RRM3 contributes to <a href="/facts/Dimerization/UFIw0Ua1">dimerization</a> and <a href="/facts/Oligomerization/v7oDY8zu">oligomerization</a> of HuR, supporting binding to AU-rich elements of RNA by the other domains, but RRM3 itself has moderate binding strength to RNA.<a class="footnote-ref" id="fnref:13" href="#fn:13">13</a> RRM3 has been shown to bind to long <a href="/facts/Polyadenylation/ILnXUBKP">poly-A tails</a> and AU-rich RNAs.<a class="footnote-ref" id="fnref:14" href="#fn:14">14</a>

<h2 id="function">Function</h2>
This RNA-binding protein has been found to be involved in a number of valuable cellular processes in mammals, including embryonic development, stress responses, and the immune system.<a class="footnote-ref" id="fnref:15" href="#fn:15">15</a> Post-translational modifications of HuR, including <a href="/facts/Phosphorylation/LXUEEeIL">phosphorylation</a>, <a href="/facts/Neddylation/INuFfyfN">NEDDylation</a>, <a href="/facts/Methylation/EvDMWVW5">methylation</a>, and <a href="/facts/Ubiquitination/hpulmU3m">ubiquitination</a> each modulate the localization and expression of the protein in unique ways. Modifications such as methylation and ubiquitination alter the <a href="/facts/Affinity_(biochemistry)/44QLL4eU">affinity</a> of HuR to RNA.<a class="footnote-ref" id="fnref:16" href="#fn:16">16</a> As an important regulator of post-transcriptional regulation, HuR destabilization from the mRNA is associated with degradation of the transcript.<a class="footnote-ref" id="fnref:17" href="#fn:17">17</a>
Phosphorylation of HuR can occur by <a href="/facts/Cyclin-dependent_kinase/ppYkzTaR">cyclin-dependent kinases</a> (cdks), impacting its localization within the cell in a cell cycle-dependent fashion.<a class="footnote-ref" id="fnref:18" href="#fn:18">18</a> Additionally, checkpoint kinase 2 plays a significant role in phosphorylating HuR during <a href="/facts/Genotoxicity/fRUJaqxo">genotoxic</a> stress, promoting dissociation of HuR from its target mRNA transcript.<a class="footnote-ref" id="fnref:19" href="#fn:19">19</a>
Additionally, the ubiquitination of HuR by an <a href="/facts/E3_ligase/8xmNaWW3">E3 ligase</a> in many cases results in <a href="/facts/Proteasomal_degradation/8vTtg2MI">proteasomal degradation</a>. For instance, the esophageal tumor suppressor ECRG2, ubiquitinates HuR during DNA damage, promoting its degradation.<a class="footnote-ref" id="fnref:20" href="#fn:20">20</a> However, in other cases, ubiquitination promotes dissociation of HuR from its transcript, such as ubiquitination of certain <a href="/facts/Lysine/CEetgA9L">lysine</a> residues of the RRM3 domain leading to detachment from the mRNA transcript of <a href="/facts/P21/gb0VLtY8">P21</a> and other tumor suppressors.<a class="footnote-ref" id="fnref:21" href="#fn:21">21</a>
Moreover, as is frequent in other mammalian proteins, HuR is methylated at arginine residues.<a class="footnote-ref" id="fnref:22" href="#fn:22">22</a> For instance, protein arginine <a href="/facts/Methyltransferase/MIpCDLdh">methyltransferase</a> enzymes (PRMTs) methylate HuR to promote mRNA stabilization of certain target transcripts, such as <a href="/facts/Sirtuin_1/LVv2lNtt">SIRT1</a> in <a href="/facts/HeLa/aP1fIhVX">HeLa</a> cells.<a class="footnote-ref" id="fnref:23" href="#fn:23">23</a>
HuR has been shown to inhibit biogenesis of <a href="/facts/MIR7-1/tKjWCRk1">miR-7</a>.<a class="footnote-ref" id="fnref:24" href="#fn:24">24</a><a class="footnote-ref" id="fnref:25" href="#fn:25">25</a> Small molecules have been shown to target HuR/RNA interactions with a functional outcome on the downstream targets.<a class="footnote-ref" id="fnref:26" href="#fn:26">26</a><a class="footnote-ref" id="fnref:27" href="#fn:27">27</a>

<h2 id="cancer">Cancer</h2>
Although HuR has a vital role in <a href="/facts/Transcriptome/h6CC0sR5">transcriptosomal</a> regulation, there is an apparent up-regulation of HuR in several types of cancer that correlates with a malignant or metastatic status that has increased the relevance of HuR as a potential therapeutic target for a number of cancer studies. The abundance of HuR suggests a tumorigenic promotion of <a href="/facts/Angiogenesis/h0HF9IUd">angiogenesis</a>, cellular proliferation, and anti-<a href="/facts/Apoptosis/8dVzSm4y">apoptotic</a> properties in cancer cells, purportedly due to the impact of mRNA stabilization and its ubiquitous presence in human tissue.<a class="footnote-ref" id="fnref:28" href="#fn:28">28</a>

<h2 id="inhibitors">Inhibitors</h2>
<ul><li>CMLD-2</li>
<li>KH-3</li>
<li>SRI-42127</li></ul>

<h2 id="external-links">External links</h2>
<ul><li><a href="https://www.ebi.ac.uk/pdbe/pdbe-kb/proteins/Q15717">PDBe-KB</a> provides an overview of all the structure information available in the PDB for Human ELAV-like protein 1</li></ul>
This article incorporates text from the <a href="/facts/United_States_National_Library_of_Medicine/Hzty0MCX">United States National Library of Medicine</a> (<a href="https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=1994">[1]</a>), which is in the <a href="/facts/Public_domain/YWKMDKw4">public domain</a>.

<h2 id="references">References</h2>

<ol>
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</ol>

ELAV-like protein 1 open-in-new

ELAV-like protein 1