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

Area of Science:

• Molecular Biology
• Genomics
• RNA Biology

Background:

• ZFP36L2 (zinc finger protein 36 like 2) is an RNA-binding protein that targets adenine-uridine-rich elements (AREs) in transcripts.
• Previous studies suggested ZFP36L2 has specific transcript preferences, but this was limited to a few tissues.
• Understanding ZFP36L2's tissue-specific activity is crucial for elucidating its regulatory roles.

Purpose of the Study:

• To investigate the tissue-specific transcript selectivity of ZFP36L2.
• To identify the mechanisms underlying ZFP36L2's tissue-specific targeting using a knock-out mouse model.
• To explore ZFP36L2 binding sites and preferences.

Main Methods:

• Differential expression transcriptomic analysis in six tissues (lung, liver, bone marrow, spleen, kidney, ovary) of Zfp36l2 knock-out mice.
• Analysis of up-regulated ARE-transcripts to identify ZFP36L2 targets.
• Enhanced Cross-Linking and ImmunoPrecipitation (eCLIP) followed by AU-Rich Element (ARE) score analysis to determine binding sites.

Main Results:

• ZFP36L2 exhibits significant tissue-specific targeting of ARE-transcripts, with only Apol11b consistently upregulated across all studied tissues.
• Up-regulated genes in Zfp36l2-deficient mice were enriched in protein-coding genes, particularly immunoglobulin V (IgV) genes.
• eCLIP data and AREscore analysis confirmed ZFP36L2 binding to AREs, with some variations in flanking sequence composition.

Conclusions:

• ZFP36L2 plays a critical role in tissue-specific post-transcriptional regulation by targeting specific ARE-containing transcripts.
• The findings highlight the complex regulatory network governed by ZFP36L2 and its potential involvement in immune system regulation.
• Further research into ZFP36L2's functions in different tissues may reveal novel therapeutic targets.