Integrator complex subunit 15 controls mRNA splicing and is critical for eye development.

Area of Science:

• Molecular Biology
• Genetics
• Developmental Biology

Background:

• Eye and brain development rely on precise gene expression.
• Transcription factors and developmental regulators are key.
• Hereditary eye diseases can stem from genetic mutations.

Purpose of the Study:

• To characterize Integrator complex subunit 15 (INTS15).
• To identify the genetic cause of an autosomal-dominant eye disease.
• To elucidate the role of INTS15 in ocular and neural development.

Main Methods:

• Molecular and genetic characterization of INTS15.
• Analysis of knockout and mutant mice models.
• Investigation using human induced pluripotent stem cell (iPSC)-derived neural progenitor cells.

Main Results:

• INTS15 interacts with the Integrator complex, supporting small nuclear RNA 3' end processing.
• INTS15 knockdown causes widespread gene missplicing and affects genes critical for eye and brain development.
• INTS15 is essential for axonal outgrowth in retinal ganglion cells.

Conclusions:

• INTS15 is critical for normal eye and brain development.
• Defects in INTS15 contribute to hereditary eye diseases.
• This study reveals a link between transcription machinery and specific hereditary disorders.