Cell | Jun Liu's Team Develops FOCAS Platform for Transcriptome-wide Functional Analysis of m⁶A Sites

Recently, Prof. Jun Liu's team at SRILS published a research paper titled "Functional m6A Sites Detection by CRISPR-dCas13b-FTO Screening" in the journal Cell.

The study introduces FOCAS, an innovative platform designed for transcriptome-wide functional analysis of N6-methyladenosine (m6A) sites.

Background

m6A is the most abundant internal modification in eukaryotic mRNA, playing critical roles in RNA splicing, stability, and translation. However, traditional methods lack the resolution to distinguish the functional differences of specific m6A sites, limiting our understanding of its fine regulatory logic.

Key Technology: FOCAS Platform

Based on the CRISPR-dCas13b system, FOCAS precisely targets the demethylase FTO to specific RNA regions. It achieves targeted demethylation without altering the RNA sequence or affecting global m6A levels.

• Single-base Precision: The first platform enabling transcriptome-wide functional screening at single-base resolution.
• Broad Coverage: Applicable to both mRNA and non-coding RNA.
• Zero Confusion: Avoids the confounding effects of traditional mutagenesis methods.

Major Findings

Using a massive library of 204,832 sgRNAs targeting 12,118 genes, the team identified 4,475 functional genes regulated by m6A that significantly impact cancer cell proliferation. These findings reveal that the m6A regulatory network in cancer cells is far more extensive than previously thought.