Work

Premature cleavage and polyadenylation in the minor intron of PTEN modulate its expression and generate a functional long non-coding RNA

Year: 2026

Type: article

Abstract: The tumor suppressor, PTEN, contains a minor intron (mi-INTs) at the start of the gene. mi-INTs regulate the expression of their host genes because their inefficient splicing can be rate-limiting. Whether the PTEN mi-INTs regulate PTEN expression is unclear. PTEN levels are tightly controlled in cancer cells, especially breast cancer, since small reductions promote tumorigenesis. Cancer cells, therefore, employ numerous mechanisms to reduce PTEN. Here, we describe a previously unexplored mechanism that modulates PTEN through its mi-INT. In breast cancer cells, this intron shows low splicing efficiency, causing about half of the PTEN pre-mRNA to retain it and fail to produce functional protein. Unlike many mi-INTs that act as reversible molecular switches, this intron is irreversibly processed by premature cleavage and polyadenylation to generate a long noncoding RNA, PINC. Exogenous PINC alters endogenous PTEN protein levels and cellular proliferation, even in PTEN-mutant cells, indicating PTEN- dependent and independent functions.

Source: iScience

DOI: 10.1016/j.isci.2026.115726

Authors: Mariam Elesnawy, Rim Elghandour, Hana Hasna, Aisha Fakhroo, Boshra Al-Sulaiti, Ihab Younis

Institutions: Carnegie Mellon University Qatar, Carnegie Mellon University

Language: English

Topic: RNA Research and Splicing

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,240