Long noncoding RNA complementarity and target transcripts abundance

• Published in: Biochimica et biophysica acta Vol. 1861; no. 3; pp. 224 - 234
• Main Authors: Zealy, Richard W., Fomin, Mikhail, Davila, Sylvia, Makowsky, Daniel, Thigpen, Haley, McDowell, Catherine H., Cummings, James C., Lee, Edward S., Kwon, Sang-Ho, Min, Kyung-Won, Yoon, Je-Hyun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2018
• Subjects: Animals; Base Sequence; Chromosomal Proteins, Non-Histone - metabolism; Gene Expression Regulation; Gene Silencing; HeLa Cells; Humans; Mice; Repetitive Sequences, Nucleic Acid - genetics; RNA Stability - genetics; RNA, Antisense - genetics; RNA, Antisense - metabolism; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism
• ISSN: 1874-9399; 0006-3002; 1876-4320; 1878-2434
• DOI: 10.1016/j.bbagrm.2018.02.001

Eukaryotic mRNA metabolism regulates its stability, localization, and translation using complementarity with counter-part RNAs. To modulate their stability, small and long noncoding RNAs can establish complementarity with their target mRNAs. Although complementarity of small interfering RNAs and microRNAs with target mRNAs has been studied thoroughly, partial complementarity of long noncoding RNAs (lncRNAs) with their target mRNAs has not been investigated clearly. To address that research gap, our lab investigated whether the sequence complementarity of two lncRNAs, lincRNA-p21 and OIP5-AS1, influenced the quantity of target RNA expression. We predicted a positive correlation between lncRNA complementarity and target mRNA quantity. We confirmed this prediction using RNA affinity pull down, microarray, and RNA-sequencing analysis. In addition, we utilized the information from this analysis to compare the quantity of target mRNAs when two lncRNAs, lincRNA-p21 and OIP5-AS1, are depleted by siRNAs. We observed that human and mouse lincRNA-p21 regulated target mRNA abundance in complementarity-dependent and independent manners. In contrast, affinity pull down of OIP5-AS1 revealed that changes in OIP5-AS1 expression influenced the amount of some OIP5-AS1 target mRNAs and miRNAs, as we predicted from our sequence complementarity assay. Altogether, the current study demonstrates that partial complementarity of lncRNAs and mRNAs (even miRNAs) assist in determining target RNA expression and quantity. •Global changes of lncRNAs target mRNA abundance are measured.•Human lincRNA-p21 regulates the abundance of a subset of target mRNAs in complementary dependent manner.•Mouse lincRNA-p21 does not regulate the abundance of target mRNAs based on sequence complementarity.•Human OIP5-AS1 regulates the abundance of target mRNAs by stabilizing them.•LncRNAs modulates the abundance of many target mRNAs in complementary-dependent and independent manner.