On the occasion of the 20th anniversary of the RNA journal.

Abstract

On the wonderful occasion of the RNA journal's 20th anniversary, I think one can say without a doubt that the RNA field has been an amazing source of excitement and remarkable advances that have inseminated multiple fields across biology and medicine. The RNA journal reflects the vibrant and collegial RNA community, but the journal's success is also a tribute to the superb leadership, integrity, and scholarship of its Editor, Tim Nilsen, and dedicated Editorial Board. I feel very fortunate to have been working in this exciting field no less because of the many friendships I have made with wonderful colleagues and mostly the truly exceptional individuals that I have had in my laboratory. The journey, so far, has been phenomenal and full of surprises. Looking back, I would not have been able to foresee the course that my laboratory took since the journal's inception. I will briefly describe some highlights that stand out in my mind from our own research and how we got there. I regret that the concise format precludes mentioning the major contributions and influence that others have had on our work—they are many! My laboratory has a long-standing interest in RNA-binding proteins, RNA-protein complexes (RNPs), and their roles in gene regulation and disease. Most gene regulation in complex eukaryotes occurs post-transcriptionally and is mediated by RNA-binding proteins and small noncoding RNAs. To produce mRNA, the primary gene transcripts of the majority of protein coding genes (pre-mRNAs; historically hnRNAs) are extensively processed to remove translation open reading frame-disrupting introns by splicing, and by 5′-end capping and 3′-end cleavage and polyadenylation (CPA). Splicing is mediated by the spliceosome, comprised of non-coding small nuclear RNPs (major: U1, U2, U4, U5, U6; minor: U11, U12, U4atac, U6atac) and protein factors. The majority of pre-mRNAs have multiple introns, each with 5′- and 3′-splice sites (ss) and multiple polyadenylation signals (PASs) that can be utilized in various alternative combinations to produce diverse mRNA and protein isoforms from the same gene. Pre-mRNA processing initiates co-transcriptionally and completes in the nucleus. The mRNAs are then transported to the cytoplasm where they can be translated and are subsequently degraded. Each of these events is regulated in a cell type and cell cycle stage-dependent manner and in response to external cues. All these processes, including recognition of constitutive and alternative pre-mRNA processing signals, depend on RNA-binding proteins (RBPs or RNP proteins).