During oocyte maturation and early development, mRNAs receive poly(A) in the cytoplasm at distinct times relative to one another and to the cell cycle. These cytoplasmic polyadenylation reactions do not occur during oogenesis, but begin during oocyte maturation and continue throughout early development. In this report, we focus on the link between cytoplasmic polyadenylation and control of the cell cycle during meiotic maturation. Activation of maturation promoting factor, a complex of CDK1 and cyclin, is required for maturation and dependent on c-mos protein kinase. We demonstrate here that two classes of polyadenylation exist during oocyte maturation, defined by their dependence of c-mos and CDK1 protein kinases. Polyadenylation of the first class of mRNAs (class I) is independent of c-mos and CDK1 kinase activities, whereas polyadenylation of the second class (class II) requires both of these activities. Class I polyadenylation, through its effects on c-mos mRNA, is required for class II polyadenylation. cis-acting elements responsible for this distinction reside in the 3'-untranslated region, upstream of the polyadenylation signal AAUAAA. Cytoplasmic polyadenylation elements (CPEs) are sufficient to specify class I polyadenylation, and subtle changes in the CPE can substantially, though not entirely, shift an RNA from class I to class II. Activation of class I polyadenylation events is independent of hyperphosphorylation of CPE-binding protein or poly(A) polymerase, and requires cellular protein synthesis. The two classes of polyadenylation and of mRNA define a dependent pathway, in which polyadenylation of certain mRNAs requires the prior polyadenylation of another. We propose that this provides one method of regulating the temporal order of polyadenylation events, and links polyadenylation to the control of the meiotic cell cycle.

Background: Nucleolin (NCL) is a multifunctional nucleolar DNAand RNA-binding protein involved in multiple intracellular processes -including chromatin remodeling, DNA recombination and replication, rRNA synthesis and processing, and mRNA transcription and metabolism -, several of which are dysregulated in hematologic malignancies. It is overexpressed on the cytoplasm and cell surface of highly proliferative cells, including several solid tumors, such as gastric, colorectal, breast, lung and hepatocellular carcinomas, and gliomas and ependymomas. In these neoplasms, overexpression increases with histologic grade, metastatic potential and clinical stage, and is a biomolecular marker of event-free survival (EFS), relapse-free survival and overall survival (OS). NCL is also overexpressed in acute myeloid leukemia (AML) blast cells, and upregulates oncogenes and downregulates tumor suppressors in both acute and chronic leukemias. In a small heterogeneous set of AML patients (pts), higher levels of NCL were found to associate with decreased OS, a finding that was echoed in a small series of diffuse large B cell lymphoma (DLBCL) pts. The prognostic (Px) value of NCL overexpression in other hematologic neoplasms is unclear.