RNA in chromatin organization and nuclear architecture

Chromatin is surrounded by various types of nuclear bodies, including the nucleolus, Cajal bodies, paraspeckles, and nuclear speckles [1]. Notably, nuclear RNA is regarded as playing a role in shaping these structures [2]. Noncoding RNAs (ncRNAs) are transcripts that are not translated into proteins. Protein-coding regions occupy less than 1.5% of the genome, while more than 75% of it is transcribed. It is estimated that over 100 000 kinds of ncRNAs are expressed in cells [3]. Many ncRNAs reside in the nucleus and are expressed in tissue-, differentiation-, and developmental-stage-specific manners. The following classifications for ncRNAs were recently proposed [4]: (1) short RNAs below 50 nucleotides (including piRNAs and miRNAs), (2) transcripts produced by RNA polymerase III (including tRNAs) and 50–500 nucleotide RNAs transcribed by RNA polymerase II (Pol II), and (3) RNAs longer than 500 nucleotides. In this review, we focus on the third category that includes the so-called long noncoding RNAs (lncRNAs), and their role in chromatin and nuclear architecture.

LncRNAs are generally less conserved among species, and expressed at low levels [5]. The modest expression of lncRNAs ensures their functional specificity toward target molecules [6], although there are exceptions such as nuclear paraspeckle assembly transcript 1 (NEAT1) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), which are ubiquitously and highly expressed. Many lncRNAs are involved in chromatin regulation by recruiting chromatin-modifying proteins [7], and possess distinct properties that make them potential architectural elements in chromatin organization. For instance, they can form secondary structures, creating unique domains for interacting with specific proteins and other RNA molecules. A single lncRNA can act as an RNA scaffold to facilitate interactions between proteins 8, 9. We will highlight the roles of lncRNAs in chromatin organization and nuclear architecture in this review.

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