Pre-NOTCH Transcription and Translation

MicroRNAs play an important negative role in translation and/or stability of NOTCH mRNAs. MicroRNAs miR-34 (miR-34A, miR-34B and mi-R34C), whose transcription is directly induced by the tumor suppressor protein p53 bind and negatively regulate translation of NOTCH1 mRNA and NOTCH2 mRNA. NOTCH1 mRNA translation is also negatively regulated by microRNAs miR-200B and miR-200C, as well as miR-449A, miR-449B and miR-449C. Translation of NOTCH3 mRNA is negatively regulated by microRNAs miR-150 and miR-206. Translation of NOTCH4 mRNA is negatively regulated by microRNAs miR-181C and miR-302A.

The NOTCH2NL

(Notch homolog 2 N-terminal-like) gene family includes four genes, NOTCH2NLA (Notch homolog 2 N-terminal-like A), NOTCH2NLB (Notch homolog 2 N-terminal-like B), NOTCH2NLC (Notch homolog 2 N-terminal-like), and NOTCH2NLR (Notch homolog 2 N-terminal-like R), which originated from the partial duplication of the first four exons and introns of the NOTCH2 gene and function to modulate NOTCH signaling.

Nascent NOTCH peptides are co-translationally targeted to the endoplasmic reticulum for further processing, followed by modification in the Golgi apparatus, before trafficking to the plasma membrane. Endoplasmic reticulum calcium ATPases, positively regulate NOTCH trafficking, possibly by contributing to accurate folding of NOTCH precursors.