Ricerc@Sapienza

The Wilms tumor 1 (WT1)-associated protein (WTAP) is upregulated in many tumours,
including, acute myeloid leukemia (AML), where it plays an oncogenic role by interacting with
different proteins involved in RNA processing and cell proliferation. In addition, WTAP is also
a regulator of the nuclear complex required for the deposition of N6-Methyladenosine (m6A)
into mRNAs, containing the METTL3 methyltransferase. However, it is not clear if WTAP
may have m6A-independent regulatory functions that might contribute to its oncogenic role.

We are currently assisting in the explosion of epitranscriptomics, which studies the functional role of chemical modifications into RNA molecules. Among more than 100 RNA modifications, the N6-methyladenosine (m⁶A), in particular, has attracted the interest of researchers all around the world. m⁶A is the most abundant internal chemical modification in mRNA, and it can control any aspect of mRNA post-transcriptional regulation.

RNA chemical modifications in coding and non-coding RNAs have been known for decades. They are generally installed by specific enzymes and, in some cases, can be read and erased by other specific proteins. The impact of RNA chemical modifications on gene expression regulation and the reversible nature of some of these modifications led to the birth of the word epitranscriptomics, in analogy with the changes that occur on DNA and histones.

Recent studies have uncovered an important role for RNA modifications in gene expression regulation, which led to the birth of the epitranscriptomics field. It is now acknowledged that RNA modifiers play a crucial role in the control of differentiation of stem and progenitor cells and that changes in their levels are a relevant feature of different types of cancer. To date, among more than 160 different RNA chemical modifications, the more relevant in cancer biology is the reversible and dynamic N6-methylation of adenosine, yielding N6-methyladenosine (m6A).