Getting to the bottom of lncRNA mechanism: structure–function relationships

Sanbonmatsu, Karissa Y.

doi:10.1007/s00335-021-09924-x

Cited by 18 publications

(12 citation statements)

References 165 publications

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“…2. The determination of lncRNA localization, structure-function relationships and interactions using a range of sequencing, chemical probing, imaging methods [430][431][432][433] and cryogenic electron microscopy 434 . 3.…”

Section: Inactivation Centrementioning

confidence: 99%

Long non-coding RNAs: definitions, functions, challenges and recommendations

Mattick

Amaral

Carninci

et al. 2023

Nat Rev Mol Cell Biol

706

384

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Genes specifying long non-coding RNAs (lncRNAs) occupy a large fraction of the genomes of complex organisms. The term 'lncRNAs' encompasses RNA polymerase I (Pol I), Pol II and Pol III transcribed RNAs, and RNAs from processed introns. The various functions of lncRNAs and their many isoforms and interleaved relationships with other genes make lncRNA classification and annotation difficult. Most lncRNAs evolve more rapidly than protein-coding sequences, are cell type specific and regulate many aspects of cell differentiation and development and other physiological processes. Many lncRNAs associate with chromatin-modifying complexes, are transcribed from enhancers and nucleate phase separation of nuclear condensates and domains, indicating an intimate link between lncRNA expression and the spatial control of gene expression during development. lncRNAs also have important roles in the cytoplasm and beyond, including in the regulation of translation, metabolism and signalling. lncRNAs often have a modular structure and are rich in repeats, which are increasingly being shown to be relevant to their function. In this Consensus Statement, we address the definition and nomenclature of lncRNAs and their conservation, expression, phenotypic visibility, structure and functions. We also discuss research challenges and provide recommendations to advance the understanding of the roles of lncRNAs in development, cell biology and disease. Sections Consensus statement Purpose of this Consensus StatementIn this Consensus Statement we present a current and coherent picture of the roles of lncRNAs in cell and developmental biology, identify the key issues in understanding their functions and chart the path forward. We address lncRNA definition, nomenclature, conservation, expression, phenotypic visibility, functional assays and molecular mechanisms encompassing lncRNA connections to chromatin architecture, epigenetic processes, enhancer function and biomolecular condensates, as well as the roles of lncRNAs outside the nucleus. We argue that loci expressing lncRNAs should be recognized as bona fide genes and discuss lncRNA structure-function relationships as the means to parse mechanisms and pathways. Finally, we identify the current challenges and offer recommendations for understanding the relationship of lncRNAs to genome architecture, gene regulation and cellular organization.The authors of this Consensus Statement were suggested by recommendations of colleagues. Consensus was reached by group e-mail and discussion. Definition and nomenclature of lncRNAslncRNAs have been arbitrarily defined as non-coding transcripts of more than 200 nucleotides (200 nt), which is a convenient size cutoff in biochemical and biophysical RNA purification protocols that deplete most infrastructural RNAs, such as 5S rRNAs, tRNAs, snRNAs and snoRNAs, as well as miRNAs, siRNAs and piRNAs 23 . This definition also excludes some other well-known short RNAs such as the primatespecific snaRs (~80-120 nt), which associate with nuclear factor 90 (ref. 24); Y ...

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Section: Inactivation Centrementioning

confidence: 99%

Long non-coding RNAs: definitions, functions, challenges and recommendations

Mattick

Amaral

Carninci

et al. 2023

Nat Rev Mol Cell Biol

706

384

View full text Add to dashboard Cite

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“…The flexibility and tendency towards being unfolded for single-stranded regions creates difficulty in visualising an RNA structure absolutely which would require additional SAXS optimisation methods to represent ( 108 , 109 ). Despite this, SAXS still remains the primary choice for visualising lncRNA, which can be further supplemented by atomic force microscopy (AFM) since they are too flexible for X-ray crystallography ( 110 ). Consequently, the impact of ssRNA regions being flexible is limited to the 5′-adenyl/3′-uridyl tails and central linker, with the former generally wrapping around its most proximate arm.…”

Section: Discussionmentioning

confidence: 99%

Biophysical characterisation of human LincRNA-p21 sense and antisense Alu inverted repeats

D’Souza

Mrozowich

Badmalia

et al. 2022

Nucleic Acids Research

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Human Long Intergenic Noncoding RNA-p21 (LincRNA-p21) is a regulatory noncoding RNA that plays an important role in promoting apoptosis. LincRNA-p21 is also critical in down-regulating many p53 target genes through its interaction with a p53 repressive complex. The interaction between LincRNA-p21 and the repressive complex is likely dependent on the RNA tertiary structure. Previous studies have determined the two-dimensional secondary structures of the sense and antisense human LincRNA-p21 AluSx1 IRs using SHAPE. However, there were no insights into its three-dimensional structure. Therefore, we in vitro transcribed the sense and antisense regions of LincRNA-p21 AluSx1 Inverted Repeats (IRs) and performed analytical ultracentrifugation, size exclusion chromatography, light scattering, and small angle X-ray scattering (SAXS) studies. Based on these studies, we determined low-resolution, three-dimensional structures of sense and antisense LincRNA-p21. By adapting previously known two-dimensional information, we calculated their sense and antisense high-resolution models and determined that they agree with the low-resolution structures determined using SAXS. Thus, our integrated approach provides insights into the structure of LincRNA-p21 Alu IRs. Our study also offers a viable pipeline for combining the secondary structure information with biophysical and computational studies to obtain high-resolution atomistic models for long noncoding RNAs.

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“…LncRNAs are over 200 nucleotides in length, polyadenylated, selectively spliced, low in abundance and have a relatively low sequence conservation. LncRNAs mainly exist in mammalian epigenetic systems ( 29 , 30 ). LncRNAs are mainly located in the nucleus or cytoplasm ( 31 , 32 ).…”

Section: Structure and Function Of Lncrnasmentioning

confidence: 99%

“…The lncRNA structure is more complex than that of mRNA but simpler than that of rRNA ( 36 , 37 ). Through the determination of the secondary structure of lncRNAs, lncRNAs can be divided into the following groups: 1. highly structured RNAs with subdomains and complex structural motifs; 2. loose RNA with multiple stem rings, but lacking a hierarchical domain and complex motifs; 3. unstructured and disordered RNA, lacking secondary structure ( 29 ). Currently, there are few studies on the tertiary structure of lncRNA, and the specific structure is not very clear.…”

Section: Structure and Function Of Lncrnasmentioning

confidence: 99%

The Role of LncRNAs in the Regulation of Radiotherapy Sensitivity in Cervical Cancer

et al. 2022

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Cervical cancer (CC) is one of the three majors gynecological malignancies, which seriously threatens women’s health and life. Radiotherapy (RT) is one of the most common treatments for cervical cancer, which can reduce local recurrence and prolong survival in patients with cervical cancer. However, the resistance of cancer cells to Radiotherapy are the main cause of treatment failure in patients with cervical cancer. Long non-coding RNAs (LncRNAs) are a group of non-protein-coding RNAs with a length of more than 200 nucleotides, which play an important role in regulating the biological behavior of cervical cancer. Recent studies have shown that LncRNAs play a key role in regulating the sensitivity of radiotherapy for cervical cancer. In this review, we summarize the structure and function of LncRNAs and the molecular mechanism of radiosensitivity in cervical cancer, list the LncRNAs associated with radiosensitivity in cervical cancer, analyze their potential mechanisms, and discuss the potential clinical application of these LncRNAs in regulating radiosensitivity in cervical cancer.

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Getting to the bottom of lncRNA mechanism: structure–function relationships

Cited by 18 publications

References 165 publications

Long non-coding RNAs: definitions, functions, challenges and recommendations

Long non-coding RNAs: definitions, functions, challenges and recommendations

Biophysical characterisation of human LincRNA-p21 sense and antisense Alu inverted repeats

The Role of LncRNAs in the Regulation of Radiotherapy Sensitivity in Cervical Cancer

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