# Discovery of novel murine PML isoforms

## TL;DR

The study identifies a new mouse PML isoform and explores the roles of various PML variants in forming nuclear bodies and their behavior under stress.

## Contribution

Discovery of a novel murine PML isoform, mPMLX7, and its distinct structural and functional characteristics.

## Key findings

- Mice express five predicted PML variants and a novel isoform, mPMLX7, with unique RBCC domain splicing.
- mPMLX7 is enriched in the nucleoplasm and adopts a stable conformation, suggesting a specialized function.
- Most PML isoforms form nuclear bodies and are degraded by arsenic, except mPMLX7.

## Abstract

Promyelocytic leukemia protein (PML) orchestrates the formation of PML nuclear bodies (PML NBs), membraneless organelles with diverse regulatory roles. Despite their importance, the specific functions of individual PML splicing variants remain unclear, particularly in murine models. Here we study the repertoire of murine PML isoforms expressed in mouse tissues and cells. We demonstrate that in addition to canonical mPML1–3, mice express five predicted variants (mPMLX1, mPMLX2, mPMLX4–X6) and a novel isoform, mPMLX7, distinguished by unique RBCC domain splicing. All isoforms exhibit distinct turnover kinetics at endogenous PML NBs. In PML-knockout cells, all isoforms except mPMLX7 form NBs de novo and are degraded upon arsenic exposure. Molecular dynamics simulations suggest mPMLX7 adopts a stable conformation; furthermore, this isoform is enriched in the nucleoplasm, suggesting a specialized function. Altogether, this isoform-resolved PML system provides a relevant model for dissecting the wide spectrum of PML-associated processes.