hnRNPs affect several aspects of the cell cycle by recruiting,
splicing, and co-regulating certain cell cycle control proteins. Much of hnRNPs' importance to cell cycle control is evidenced by its role as an oncogene, in which a loss of its functions results in various common cancers. Often, misregulation by hnRNPs is due to splicing errors, but some hnRNPs are also responsible for recruiting and guiding the proteins themselves, rather than just addressing nascent RNAs.
BRCA1 hnRNP C is a key regulator of the
BRCA1 and
BRCA2 genes. In response to ionizing radiation, hnRNP C partially localizes to the site of DNA damage, and when depleted,
S-phase progression of the cell is impaired. Additionally, BRCA1 and BRCA2 levels fall when hnRNP C is lost. BRCA1 and BRCA2 are crucial tumor-suppressor genes which are strongly implicated in breast cancers when mutated. BRCA1 in particular causes
G2/M cell cycle arrest in response to DNA damage via the
CHEK1 signaling cascade. hnRNP C is important for the proper expression of other tumor suppressor genes including RAD51 and BRIP1 as well. Through these genes, hnRNP is necessary to induce cell-cycle arrest in response to DNA damage by
ionizing radiation. HER2 is an upstream regulator of cyclin D1 and p27, and its overexpression leads to the deregulation of the
G1/S checkpoint.
p53 hnRNPs also play a role in DNA damage response in coordination with
p53.
hnRNP K is rapidly induced after DNA damage by ionizing radiation. It cooperates with p53 to induce the activation of p53 target genes, thus activating cell-cycle checkpoints. p53 itself is an important
tumor-suppressor gene sometimes known by the epithet "the guardian of the genome." hnRNP K's close association with p53 demonstrates its importance in DNA damage control. p53 regulates a large group of RNAs that are not translated into protein, called large intergenic noncoding RNAs (
lincRNAs). p53 suppression of genes is often carried out by a number of these lincRNAs, which in turn have been shown to act though hnRNP K. Through physical interactions with these molecules, hnRNP K is targeted to genes and transmits p53 regulation, thus acting as a key repressor within the p53-dependent transcriptional pathway. ==Functions==