| hnRNP L belongs to the heterogeneous nuclear ribonucleoprotein family essential for coordinating pre-mRNA processing pathways including splicing, polyadenylation, and mRNA export to the cytoplasm. The protein incorporates four RNA recognition motifs that selectively engage CA-rich and CA-repeat sequences within target transcripts, alongside proline-rich regions that mediate protein-protein interactions for complex assembly on nascent RNA. Binding to these motifs directs diverse splicing outcomes such as intron retention, cassette exon inclusion or skipping, and multi-exon suppression through combinatorial control with other regulators like PTB, while also influencing alternative poly(A) site choice to modulate 3' end formation. hnRNP L accumulates and associates with the 5' UTR of p53 mRNA, enhancing its translation via conformational adjustments that favor ribosomal scanning and initiation, thereby elevating p53 protein levels to activate downstream targets like p21 for G2/M arrest and Puma for apoptosis induction. Cytoplasmic translocation occurs under stress conditions, allowing hnRNP L to fine-tune translation of survival-related mRNAs beyond its nuclear roles. Auto- and cross-regulation maintain hnRNP L levels through splicing of its own pre-mRNA and that of paralog hnRNP LL, ensuring balanced expression across tissues. Overexpression in prostate cancer tissues correlates with advanced disease, where hnRNP L interacts with p53 mRNA to alter cyclin D1 and p21 balance, promoting S-phase progression and proliferation while inhibiting apoptosis. |
Lane 1: HepG2, Lane 2: A-673, Lane 3: NIH/3T3, Lane 4: COS7
