Zfp36l2 mm10 Knockout eCLIP Tracks for UCSC Genome Browser

ZFP36L2 (zinc finger protein 36 like 2, C3H type-ZFP) is an RNA-binding protein targeting<br>transcripts rich in adenine-uridine elements (AREs). Previous transcriptomic analysis<br>suggested that ZFP36L2 displays a distinct transcript preference, depending on the tissue<br>of expression. However, this analysis was restricted to a few tissues. Here, we collected<br>RNA-seq data in six tissues and detected a remarkable transcript selectivity. Given that<br>ZFP36L2 accelerates the degradation of specific ARE-transcripts upon binding, we<br>obtained differential expression transcriptomic data on a Zfp36l2 knock-out mouse model<br>to delve into the mechanisms governing this tissue-specific targeting. Transcriptomic<br>analyzes of up regulated ARE-transcripts in lung, liver, bone marrow, spleen, kidney, and<br>ovary of the Zfp36l2-deficient mouse confirmed that there is high tissue preference in<br>ZFP36L2 targets. We observed only one common up regulated gene, Apol11b, among<br>these six different tissues. However, we do observe common trends, specifically an<br>enrichment in protein coding genes in the up regulated genes, consistent with these RBP<br>primarily targeting genes on their 3’ UTRs. Interestingly, we observed a significant<br>increase in the proportion of IG (immunoglobulin) genes being up regulated. We further<br>performed eCLIP (Enhanced Cross-Linking&amp;ImmunoPreciptation) on a mouse cell line,<br>MLTC-1 cells, to identify direct binding sites of ZFP36L2. AU-Rich Element score<br>(AREscore) analysis revealed enrichment in both up regulated genes and eCLIP peaks,<br>although some differences were observed in flanking residue composition. Our findings<br>provide new insights into the intricate regulatory network orchestrated by ZFP36L2,<br>opening avenues for exploring its potential roles in different tissues.

ZFP36L2（锌指蛋白36同源物2，C3H型锌指蛋白（C3H type-ZFP））是一类靶向富含腺嘌呤-尿嘧啶元件（adenine-uridine elements, AREs）的RNA结合蛋白（RNA-binding protein）。既往转录组学分析显示，ZFP36L2展现出独特的转录本偏好性，且该偏好性与其表达组织相关。但此类分析仅局限于少数组织。本研究收集了6种组织的RNA测序（RNA-seq）数据，并检测到显著的转录本选择性结合特征。鉴于ZFP36L2结合后可加速特定ARE转录本的降解，我们获取了Zfp36l2基因敲除小鼠模型的差异表达转录组数据，以深入解析调控该组织特异性靶向的分子机制。
对Zfp36l2缺陷小鼠的肺、肝、骨髓、脾、肾及卵巢中上调的ARE转录本进行转录组分析，证实ZFP36L2的靶标具有高度的组织偏好性。我们在这6种不同组织中仅观察到1个共同的上调基因Apol11b。不过，我们确实发现了共同的表达趋势：上调基因中富集蛋白编码基因，这与这类RNA结合蛋白主要靶向基因3'非翻译区（3' untranslated region, 3' UTR）的特性相符。有趣的是，我们观察到免疫球蛋白（immunoglobulin, IG）基因的上调比例显著升高。
我们进一步在小鼠细胞系MLTC-1中开展了增强型交联免疫沉淀（Enhanced Cross-Linking & ImmunoPrecipitation, eCLIP）实验，以鉴定ZFP36L2的直接结合位点。腺嘌呤-尿嘧啶元件评分（AU-Rich Element score, AREscore）分析显示，上调基因及eCLIP峰中均存在ARE富集现象，尽管侧翼残基组成存在一定差异。本研究结果为ZFP36L2介导的复杂调控网络提供了全新见解，为探索其在不同组织中的潜在功能开辟了新的研究路径。