Pre-mRNA splicing imprints mRNA in the nucleus with a novel RNA-binding protein that persists in the cytoplasm

Area of Science:

• Molecular Biology
• Gene Expression
• RNA Processing

Background:

• Messenger RNA (mRNA) undergoes significant processing after transcription, including splicing, to become functional.
• The protein complexes associated with mRNA can influence its fate and function.
• Understanding the composition of these complexes is crucial for deciphering gene expression pathways.

Purpose of the Study:

• To identify and characterize novel RNA-binding proteins involved in mRNA processing and export.
• To investigate the association of the identified protein with different RNA species and its localization within the cell.
• To determine the role of this protein in the transition of mRNA from the nucleus to the cytoplasm.

Main Methods:

• Description of a novel RNA binding protein, Y14.
• Analysis of Y14 association with various RNA types (pre-mRNAs, introns, spliced mRNAs, intronless cDNAs).
• Investigation of Y14 localization (nuclear/cytoplasmic) and association with other proteins, including mRNA export factors like TAP.

Main Results:

• Y14 is a nuclear, nucleocytoplasmic shuttling protein.
• Y14 preferentially binds to spliced mRNAs, not pre-mRNAs or introns.
• Splicing of even a single intron triggers Y14 association.
• Y14 forms distinct nuclear complexes containing hnRNP proteins and the mRNA export factor TAP.
• Y14 is found on both nuclear and newly exported cytoplasmic mRNAs.

Conclusions:

• Y14 defines novel messenger ribonucleoprotein (mRNP) intermediates in gene expression: post-splicing nuclear pre-export mRNPs and newly exported cytoplasmic mRNPs.
• The composition of these mRNPs is determined by the splicing process.
• Pre-mRNA splicing imprints mRNA with a specific protein set (including Y14) that is maintained in the cytoplasm, potentially communicating the transcript's history.