The RNA binding protein ZFP36L2 displays tissue-selective mRNA targeting in mice

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

ZFP36L2 (zinc finger protein 36 like 2, C3H type-ZFP) is an RNA-binding protein targeting transcripts rich in adenine-uridine elements (AREs). Previous transcriptomic analysis suggested that ZFP36L2 displays a distinct transcript preference or 'specific activity'. However, this analysis was restricted to a few tissues. Here, using experimental data in multiple tissues we detected a remarkable transcript selectivity depending on the tissue. Given that ZFP36L2 accelerates the degradation of specific ARE-transcripts upon binding, we obtained differential expression transcriptomic data on a Zfp36l2 knock-out mouse model to delve into the mechanisms governing this tissue-specific targeting. Transcriptomic analyzes of up-regulated ARE-transcripts in six tissues, lung, liver, bone marrow, spleen, kidney, and ovary of the Zfp36l2-deficient mouse confirmed that there is high tissue preference in ZFP36L2 targets. We observed only one common up-regulated gene, Apol11b, among these six different tissues. However, we do observe common trends, specifically an enrichment in protein coding genes in the up-regulated genes, consistent with these RBP primarily targeting genes on their 3' UTRs. Interestingly, we observed a significant increase in the proportion of IgV (immunoglobulin) genes being up-regulated. We further performed eCLIP (Enhanced Cross-Linking&ImmunoPreciptation) on a mouse cell l

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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